Is ABCA2 p.Ala314Val (c.941C>T) pathogenic?

ABCA2 p.Ala314Val (c.941C>T) is classified Uncertain significance in ABCA2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-24). AlphaMissense: likely benign (0.0865); Ultra-rare (popmax 0.0351%, mid).

How common is ABCA2 p.Ala314Val (c.941C>T) in the general population?

ABCA2 p.Ala314Val (c.941C>T) is ultra-rare (popmax 0.0351%, mid) (gnomAD).

What do computational predictors say about ABCA2 p.Ala314Val (c.941C>T)?

AlphaMissense predicts likely benign (score 0.0865) — an in-silico prediction, not a clinical call.

ABCA2 p.Ala314Val

c.941C>T · rs890852182 · VCV2547448

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0865 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0351%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0865	likely benign
REVEL	0.184	benign-leaning
SaProt	LLR -7.41	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	Δ0.27	acceptor gain · deltas
Constraint at this position
Conservation	phyloP 2.6	GERP -1.4, phastCons 0.98
Regional constraint	o/e 1.07	unconstrained · MANE · 2,023 bp · p 0.16 · regional, not allelic
Overall
CADD	18.23	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM A313V vs ClinVar A314V) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0351% Middle Eastern · 2/5,694 alleles

Filtering AF 0.00616% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00255%

Overall 0.00188% 28/1,487,646 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0351%	2,847
Remaining individualsnot grpmax-eligible	0.00349%	28,635
Admixed American	0.00256%	39,028
European (non-Finnish)	0.00188%	53,220
Finnishnot grpmax-eligible	0.00177%	56,614
South Asian	0.00134%	74,400

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: ABCA2
Protein: p.Ala314Val
Coding: c.941C>T
MANE Select: NM_001606
dbSNP: rs890852182
Type: single nucleotide variant
Location: chr9:137021018 (GRCh38)
Gene constraint: LOEUF 0.436 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 71.46

Full ABCA2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ABCA2 p.Ala314= Likely benign ★★ same residue
ABCA2 p.Gln1370Ter Likely pathogenic ★★ same type
ABCA2 c.3883-3C>T Uncertain significance ★★ same type
ABCA2 p.Ala1357Thr Uncertain significance ★★ ⚠ same type
ABCA2 p.Ala1620Thr Uncertain significance ★★ ⚠ same type
ABCA2 p.Ala1645Val Uncertain significance ★★ ⚠ same type
ABCA2 p.Ala1715Ser Uncertain significance ★★ ⚠ same type
ABCA2 p.Ala2180Thr Uncertain significance ★★ ⚠ same type

Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →

Cite Sugi Variant

Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/abca2-p-ala314val (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown