# NM_145698.5(ACBD5):c.42G>A (p.Trp14Ter)

https://sugi.bio/variant/acbd5-p-trp14ter

## Summary

**ACBD5 p.Trp14Ter (c.42G>A)** is classified **Pathogenic** in ACBD5 (ClinVar, Single submitter, 1 submitter; last evaluated 2020-08-05). Very rare (popmax 0.00334%, amr).

**At a glance:** Pathogenic · review: Single submitter · rsID rs2065341675 · 1 submitter · very rare (popmax 0.00334%, amr)

## For patients & families {#patients}

This is a change in the ACBD5 gene that is reported as disease-causing, but on limited review, submitted by 1 submitter.

*Reference information, not medical advice, and not a prediction for any individual. A genetic counselor or clinician can interpret what it means for you and your family.*

**Support & next steps:** [Find a genetic counselor (NSGC)](https://findageneticcounselor.nsgc.org/).

## Identity {#identity}

| Field | Value |
| --- | --- |
| Gene | [ACBD5](https://sugi.bio/atlas/gene/ACBD5/) |
| Protein change (HGVS p.) | p.Trp14Ter |
| Coding change (HGVS c.) | c.42G>A |
| MANE Select transcript | [NM_145698](https://www.ncbi.nlm.nih.gov/nuccore/NM_145698) |
| dbSNP | [rs2065341675](https://www.ncbi.nlm.nih.gov/snp/rs2065341675/) |
| Variant type | single nucleotide variant |
| Location | chr10:27240458-27240458 (GRCh38) |
| ClinVar | [VCV1069217](https://www.ncbi.nlm.nih.gov/clinvar/variation/1069217/) |

**All HGVS expressions:** `NC_000010.10:g.27529387C>T`, `NC_000010.11:g.27240458C>T`, `NG_032960.3:g.13217G>A`, `NM_001042473.4:c.-64G>A`, `NM_001271512.3:c.36G>A`, `NM_001301251.2:c.-165G>A`, `NM_001301252.2:c.-165G>A`, `NM_001301253.2:c.-165G>A`, `NM_001301254.2:c.-165G>A`, `NM_001352568.1:c.63G>A`, `NM_001352569.1:c.42G>A`, `NM_001352570.1:c.42G>A`, `NM_001352571.1:c.36G>A`, `NM_001352572.1:c.63G>A`, `NM_001352573.1:c.42G>A`, `NM_001352574.2:c.-64G>A`, `NM_001352575.2:c.-64G>A`, `NM_001352576.2:c.-64G>A`, `NM_001352577.2:c.-64G>A`, `NM_001352578.2:c.-64G>A`, `NM_001352579.2:c.-64G>A`, `NM_001352580.2:c.-64G>A`, `NM_001352581.1:c.42G>A`, `NM_001352582.2:c.-64G>A`, `NM_001352583.1:c.-165G>A`, `NM_001352584.1:c.-165G>A`, `NM_001352585.1:c.-165G>A`, `NM_001352586.1:c.36G>A`, `NM_001352587.1:c.36G>A`, `NM_001352588.1:c.42G>A`, `NM_145698.5:c.42G>A`

## Computational & population evidence {#evidence}

**Concordance:** 1 independent predictor **concordant** with the ClinVar classification.

- **Missense predictors (AlphaMissense/REVEL/SaProt) do not apply** to this variant type — they score amino-acid substitutions only. For non-missense variants the computational signal comes from conservation and, for splice-region changes, SpliceAI (below), not from a missing predictor score.
- SpliceAI predicts **acceptor gain** (Δ 0.20) — consistent with the pathogenic call
- Conservation: phyloP 4.748, GERP 1.68, phastCons 1 — highly conserved position (PP3-type support)
- Molecular consequence: **nonsense (stop-gain)** — a predicted loss-of-function variant. Gene population constraint: LOEUF 0.734, pLI 2.2882e-06. *Descriptive; not an applied PVS1 code.*
- Nonsense-mediated decay: the premature termination codon is **in exon 2 of 13**, so the transcript is predicted to undergo NMD.
- CADD: **PHRED 42.0**. No single ClinGen-calibrated threshold exists and the expert panels that use CADD disagree — GUCY2D/AIPL1 require ≥ 20.0 for an untranslated-region variant, ABCA4 ≥ 28.1 for a synonymous or indel variant, the Pulmonary Hypertension panel imports Pejaver 2022's missense-calibrated numbers, and the Antibody Deficiencies panel declines CADD entirely for PIK3CD. CADD v1.7 also incorporates Zoonomia phyloP, so it partly re-expresses the conservation above. *Descriptive; no threshold applied.*
- SpliceAI deltas (raw): acceptor loss **0.01**, donor loss **0.00**, acceptor gain **0.20**, donor gain **0.00**. Largest is acceptor gain.
- SpliceAI deltas (masked): acceptor loss **0.00**, donor loss **0.00**, acceptor gain **0.20**, donor gain **0.00**.
- Population frequency (gnomAD v4.1): grpmax **0.00334%** (amr) · FAF95 0.000554% · FAF99 0.000207% · 2/59,852 in the highest group · 2/1,613,168 alleles overall — very rare (popmax 0.00334%, amr).

*Computational predictors are not independent (ClinGen Variant Classification guidance): AlphaMissense (Cheng et al. 2023) carries the ACMG weight for missense and conservation (phyloP/GERP/phastCons) for non-missense; REVEL (Pejaver-2022 calibrated strength bands) and SaProt (Su et al. 2023, structure-aware, ClinVar-independent protein language model, raw LLR) are shown as orthogonal agreement signals, not additive. For frequency, the gnomAD v4.1 grpmax filtering allele frequency (FAF95) is ClinGen's designated BA1/BS1 input (gnomAD v4 guidance v3.0, June 2025); BA1/BS1 thresholds are disease-specific, not a blanket 5%. Predictions, not a clinical determination.*

## Gene constraint & dosage {#gene-context}

**ACBD5** population constraint: LOEUF 0.734, pLI 2.2882e-06, missense-Z 1.6734. *Lower LOEUF and higher pLI indicate a gene that tolerates loss-of-function poorly; ClinGen dosage is the curated haploinsufficiency call.*

Curated gene–disease validity (ClinGen):

- **acyl-CoA binding domain containing protein 5 deficiency** — Definitive (AR)

## Protein context {#protein}


AlphaFold model confidence (whole protein): pLDDT 57.49, 17% of residues very-high.

**1 experimental structure(s)** (PDB): [3FLV](https://www.rcsb.org/structure/3FLV).

## What this gene does {#gene-function}

*Describes the biological roles of ACBD5 (the gene this variant disrupts) — not effects measured for this specific variant. A damaging variant is expected to affect these functions and pathways; the degree depends on the variant.*


### Pathways affected {#pathways}

ACBD5 participates in **4 Reactome pathways** (⚕ = disease pathway):

| Pathway (Reactome) | Evidence |
| --- | --- |
| [Class I peroxisomal membrane protein import](https://reactome.org/content/detail/R-HSA-9603798) | curated |
| [Peroxisomal lipid metabolism](https://reactome.org/content/detail/R-HSA-390918) | curated |
| [RHOA GTPase cycle](https://reactome.org/content/detail/R-HSA-8980692) | curated |
| [RHOC GTPase cycle](https://reactome.org/content/detail/R-HSA-9013106) | curated |

### Molecular function & processes (GO — experimentally supported) {#go}

**Biological process:** pexophagy.

## Clinical significance {#significance}

**Pathogenic** — review status Single submitter *(criteria provided, single submitter)*, last evaluated 2020-08-05.

**Submitter consensus:** unanimous (1/1 Pathogenic).

### Submitter classifications {#submitters}

| Submitter | Classification | Review | Method | Date |
| --- | --- | --- | --- | --- |
| Labcorp Genetics (formerly Invitae), Labcorp | Pathogenic | criteria provided, single submitter | clinical testing | 2020-08-05 |

**Reported phenotype names (ClinVar):** not provided, none provided.

## Similar variants {#similar}

Related ACBD5 variant pages (same residue, condition, or type): [ACBD5 p.Arg433Ter](/variant/acbd5-p-arg433ter), [ACBD5 p.Ala182Thr](/variant/acbd5-p-ala182thr), [ACBD5 p.Arg384Trp](/variant/acbd5-p-arg384trp), [ACBD5 p.Arg415Trp](/variant/acbd5-p-arg415trp), [ACBD5 p.Asp429Asn](/variant/acbd5-p-asp429asn), [ACBD5 p.Gln452His](/variant/acbd5-p-gln452his), [ACBD5 p.Glu312Lys](/variant/acbd5-p-glu312lys), [ACBD5 p.Glu493Lys](/variant/acbd5-p-glu493lys).

### Data sources & attribution {#sources}

ClinVar (NCBI — public domain, built 2026-10-14); gnomAD v4.1 (Broad Institute, built 2026-10-15); AlphaMissense (Cheng et al. 2023, © Google DeepMind — CC BY 4.0, built 2026-01-27); REVEL (Ioannidis et al. 2016 — ODbL, built 2026-07-13); SaProt (Su et al. 2023 — MIT, built 2026-10-14); SpliceAI (Illumina — free for non-commercial use, built 2026-10-13); CADD (Rentzsch et al. 2019, University of Washington — free for non-commercial use, built 2026-10-10); Conservation (phyloP/phastCons/GERP) (UCSC hg38 470-way mammal (Hiller Lab) + Ensembl Compara, built 2026-07-12); gnomAD Non-coding Constraint (Gnocchi) (Chen et al. 2024, Broad Institute — CC0, built 2026-10-11); gnomAD Regional Missense Constraint (Broad Institute — CC0, built 2026-10-13); Pangolin (Zeng & Li 2022 — CC BY 4.0, built 2026-10-11); Repeat regions (UCSC — RepeatMasker, TRF, segmental duplications, built 2026-10-11); ClinGen (ClinGen, built 2026-09-22); UniProt (CC BY 4.0); Reactome / GO (CC BY 4.0, built 2026-09-23); MaveDB (per-record license, built 2026-10-11); CIViC (CC0, built 2026-09-22); Orphanet (Orphanet, built 2026-06-12)

*Primary record: NCBI ClinVar (variation 1069217). Classifications reflect these databases as of the page's build date and may change. Free reference use — not medical advice; consult the primary submitters and a clinician.*