# NM_018358.3(ABCF3):c.1150C>T (p.Arg384Cys)

https://sugi.bio/variant/abcf3-p-arg384cys

## Summary

**ABCF3 p.Arg384Cys (c.1150C>T)** is classified **Uncertain significance** in ABCF3 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-02-12). AlphaMissense: ambiguous (0.4718); Ultra-rare (popmax 0.0164%, mid).

**At a glance:** Uncertain significance · review: Single submitter · 1 submitter · AlphaMissense ambiguous · ultra-rare (popmax 0.0164%, mid)

## For patients & families {#patients}

This is a change in the ABCF3 gene that is currently of uncertain significance — a definitive interpretation has not yet been established, 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 | [ABCF3](https://sugi.bio/atlas/gene/ABCF3/) |
| Protein change (HGVS p.) | p.Arg384Cys |
| Coding change (HGVS c.) | c.1150C>T |
| MANE Select transcript | [NM_018358](https://www.ncbi.nlm.nih.gov/nuccore/NM_018358) |
| Variant type | single nucleotide variant |
| Location | chr3:184189593-184189593 (GRCh38) |
| ClinVar | [VCV3883166](https://www.ncbi.nlm.nih.gov/clinvar/variation/3883166/) |

**All HGVS expressions:** `NC_000003.11:g.183907381C>T`, `NC_000003.12:g.184189593C>T`, `NG_054899.1:g.8519C>T`, `NM_001351298.2:c.1132C>T`, `NM_001351299.2:c.421C>T`, `NM_001351300.2:c.487C>T`, `NM_018358.3:c.1150C>T`

## Computational & population evidence {#evidence}

**Concordance:** AlphaMissense makes no call; REVEL and SaProt both call this damaging; AlphaMissense makes no call — descriptive only.

- AlphaMissense **ambiguous** (0.4718) — no call either way
- REVEL 0.882 (moderately pathogenic-leaning)
- SaProt LLR -10.29 (damaging)
- → **In-silico consensus:** REVEL and SaProt both call this damaging; AlphaMissense makes no call
- Conservation: phyloP 7.653, phastCons 1 — highly conserved
- CADD: **PHRED 33.0**. 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.*
- Regional missense constraint: **o/e 0.91** across the covering region of the MANE Select transcript (184,186,208–184,193,695), spanning 7,487 bp. Chi-square p 0.0068. Describes the region, not this allele; gnomAD v4.1.1's own constrained determination. *Descriptive; no ACMG code applied.*
- SpliceAI: **below the reporting threshold**. This position is scored for a different substitution (C>A, Δ0.53 acceptor gain), so this allele was evaluated and its deltas all fell under Δ0.2 — a prediction of no splicing effect for this allele, not a gap in our data. *No ACMG code assigned.*
- Population frequency (gnomAD v4.1): grpmax **0.0164%** (mid) · FAF95 0.000124% · FAF99 9e-05% · 1/6,084 in the highest group · 7/1,614,060 alleles overall — ultra-rare (popmax 0.0164%, mid).

| Ancestry group | Allele frequency | 1 in |
| --- | --- | --- |
| Middle Eastern (grpmax) | 0.0164% | 6,084 |
| South Asian | 0.0011% | 91,082 |
| European (non-Finnish) | 0.000424% | 236,010 |

*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}

**ABCF3** population constraint: LOEUF 0.776, pLI 1.1095e-12, missense-Z 1.3928. *Lower LOEUF and higher pLI indicate a gene that tolerates loss-of-function poorly; ClinGen dosage is the curated haploinsufficiency call.*

## Protein context {#protein}

Residue **384** lies in the abc transporter 1 domain.

AlphaFold model confidence (whole protein): pLDDT 81.77, 28% of residues very-high.

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

*Describes the biological roles of ABCF3 (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.*

**How this variant is thought to act:** ABCF3's established molecular role includes cadherin binding. p.Arg384Cys falls in the abc transporter 1 domain.


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

**Molecular function:** cadherin binding.

## Clinical significance {#significance}

**Uncertain significance** — review status Single submitter *(criteria provided, single submitter)*, last evaluated 2025-02-12.

**Submitter consensus:** unanimous (1/1 Uncertain significance).

### Submitter classifications {#submitters}

| Submitter | Classification | Review | Method | Date |
| --- | --- | --- | --- | --- |
| Ambry Genetics | Uncertain significance | criteria provided, single submitter | clinical testing | 2025-02-12 |

**Reported phenotype names (ClinVar):** not specified, AllHighlyPenetrant.

## Similar variants {#similar}

Related ABCF3 variant pages (same residue, condition, or type): [ABCF3 p.Arg384His](/variant/abcf3-p-arg384his), [ABCF3 p.Ala128Ser](/variant/abcf3-p-ala128ser), [ABCF3 p.Ala196Val](/variant/abcf3-p-ala196val), [ABCF3 p.Ala280Thr](/variant/abcf3-p-ala280thr), [ABCF3 p.Ala293Thr](/variant/abcf3-p-ala293thr), [ABCF3 p.Ala303Gly](/variant/abcf3-p-ala303gly), [ABCF3 p.Ala312Gly](/variant/abcf3-p-ala312gly), [ABCF3 p.Ala312Thr](/variant/abcf3-p-ala312thr).

### Data sources & attribution {#sources}

ClinVar (NCBI — public domain, built 2026-10-11); gnomAD v4.1 (Broad Institute, built 2026-10-06); 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 2026-07-14); 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 3883166). 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.*