# NM_019112.4(ABCA7):c.5850del (p.Asp1950fs)

https://sugi.bio/variant/abca7-p-asp1950fs

## Summary

**ABCA7 p.Asp1950fs (c.5850del)** is classified **Likely pathogenic** in ABCA7 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2023-11-07). Ultra-rare (popmax 0.0201%, sas); Associated with ABCA7-related disorder.

**At a glance:** Likely pathogenic · review: No assertion criteria · rsID rs769207938 · 1 submitter · 1 linked condition · ultra-rare (popmax 0.0201%, sas)

## For patients & families {#patients}

This is a change in the ABCA7 gene that is considered likely disease-causing, submitted by 1 submitter, and is linked to ABCA7-related disorder.

*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 | [ABCA7](https://sugi.bio/atlas/gene/ABCA7/) |
| Protein change (HGVS p.) | p.Asp1950fs |
| Coding change (HGVS c.) | c.5850del |
| MANE Select transcript | [NM_019112](https://www.ncbi.nlm.nih.gov/nuccore/NM_019112) |
| dbSNP | [rs769207938](https://www.ncbi.nlm.nih.gov/snp/rs769207938/) |
| Variant type | Deletion |
| Location | chr19:1063762-1063762 (GRCh38) |
| ClinVar | [VCV3029083](https://www.ncbi.nlm.nih.gov/clinvar/variation/3029083/) |

**All HGVS expressions:** `NC_000019.10:g.1063762del`, `NC_000019.9:g.1063761del`, `NG_046909.1:g.28660del`, `NG_139811.1:g.692del`, `NM_019112.4:c.5850del`

## 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 (below), not from a missing predictor score.
- Conservation: phyloP 6.575, GERP 1.87, phastCons 1 — highly conserved position (PP3-type support)
- Molecular consequence: **frameshift** — a predicted loss-of-function variant. Gene population constraint: LOEUF 1.368, pLI 7.922e-103. *Descriptive; not an applied PVS1 code.*
- Nonsense-mediated decay: the premature termination codon is **in exon 44 of 47**, so the transcript is predicted to undergo NMD.
- CADD: **PHRED 20.2**. 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: **not assessed** — the release is built from a substitutions-only source, so it holds no deletion variants. That is a property of the dataset, not of the variant, and is not evidence against a splicing effect.
- Population frequency (gnomAD v4.1): grpmax **0.0201%** (sas) · FAF95 0.0128% · FAF99 0.0105% · 17/84,394 in the highest group · 17/1,547,252 alleles overall — ultra-rare (popmax 0.0201%, sas).

*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}

**ABCA7** population constraint: LOEUF 1.368, pLI 7.922e-103, missense-Z -3.5932. *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 **1950** lies in the abc transporter 2 domain.

AlphaFold model confidence (whole protein): pLDDT 75.77, 11% of residues very-high.

**6 experimental structure(s)** (PDB): [8EDW](https://www.rcsb.org/structure/8EDW), [8EE6](https://www.rcsb.org/structure/8EE6), [8EEB](https://www.rcsb.org/structure/8EEB), [8EOP](https://www.rcsb.org/structure/8EOP), [8Y1O](https://www.rcsb.org/structure/8Y1O), [8Y1P](https://www.rcsb.org/structure/8Y1P) — incl. mutant structure 8EOP.

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

*Describes the biological roles of ABCA7 (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:** ABCA7's established molecular role includes obsolete phospholipid transporter activity. p.Asp1950fs falls in the abc transporter 2 domain.


### Pathways affected {#pathways}

ABCA7 participates in **1 Reactome pathway** (⚕ = disease pathway):

| Pathway (Reactome) | Evidence |
| --- | --- |
| [ABC transporters in lipid homeostasis](https://reactome.org/content/detail/R-HSA-1369062) | curated |

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

**Molecular function:** obsolete phospholipid transporter activity, apolipoprotein A-I receptor activity, phosphatidylcholine floppase activity, phosphatidylserine floppase activity, floppase activity.

**Biological process:** cholesterol efflux, phospholipid efflux, amyloid-beta formation, high-density lipoprotein particle assembly, apolipoprotein A-I-mediated signaling pathway, phospholipid translocation.

## Clinical significance {#significance}

**Likely pathogenic** — review status No assertion criteria *(no assertion criteria provided)*, last evaluated 2023-11-07.

**Submitter consensus:** unanimous (1/1 Likely pathogenic).

### Submitter classifications {#submitters}

| Submitter | Classification | Review | Method | Date |
| --- | --- | --- | --- | --- |
| PreventionGenetics, part of Exact Sciences | Likely pathogenic | no assertion criteria provided | clinical testing | 2023-11-07 |

## Associated conditions {#conditions}

[ABCA7-related disorder](https://sugi.bio/atlas/disease/abca7-related-disorder/).

**Reported phenotype names (ClinVar):** ABCA7-related disorder, ABCA7-related condition.

## Similar variants {#similar}

Related ABCA7 variant pages (same residue, condition, or type): [ABCA7 p.Phe2042fs](/variant/abca7-p-phe2042fs), [ABCA7 c.4417-7del](/variant/abca7-c-4417-minus-7del), [ABCA7 c.4417-1G>C](/variant/abca7-c-4417-minus-1g-c), [ABCA7 p.Gln1083Ter](/variant/abca7-p-gln1083ter), [ABCA7 p.Ser1135fs](/variant/abca7-p-ser1135fs), [ABCA7 p.Val898fs](/variant/abca7-p-val898fs), [ABCA7 p.Arg1754Ter](/variant/abca7-p-arg1754ter), [ABCA7 p.Glu269Ter](/variant/abca7-p-glu269ter).

### 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 3029083). 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.*