Is ACAP3 p.Cys40Tyr (c.119G>A) pathogenic?

ACAP3 p.Cys40Tyr (c.119G>A) is classified Uncertain significance in ACAP3 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-20). AlphaMissense: likely pathogenic (0.97); Very rare (popmax 0.00134%, afr).

How common is ACAP3 p.Cys40Tyr (c.119G>A) in the general population?

ACAP3 p.Cys40Tyr (c.119G>A) is very rare (popmax 0.00134%, afr) (gnomAD).

What do computational predictors say about ACAP3 p.Cys40Tyr (c.119G>A)?

AlphaMissense predicts likely pathogenic (score 0.97) — an in-silico prediction, not a clinical call.

ACAP3 p.Cys40Tyr

c.119G>A · rs762794456 · VCV3135656

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.97 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00134%, afr)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.97	likely pathogenic
REVEL	0.252	benign-leaning
SaProt	LLR -15.36	damaging
⇒ AlphaMissense and SaProt call this damaging; REVEL does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.5	GERP 2, phastCons 1
Regional constraint	o/e 1.03	unconstrained · MANE · 14 kb · p 0.33 · regional, not allelic
Overall
CADD	24.3	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00134% African / African-American · 1/74,550 alleles

Overall 0.000657% 1/152,260 alleles · very rare

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: ACAP3
Protein: p.Cys40Tyr
Coding: c.119G>A
MANE Select: NM_030649
dbSNP: rs762794456
Type: single nucleotide variant
Location: chr1:1303268 (GRCh38)
Gene constraint: LOEUF 0.816 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 76.31

Full ACAP3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ACAP3 p.Ala242Val Uncertain significance ★ ⚠ same type
ACAP3 p.Ala265Val Uncertain significance ★ ⚠ same type
ACAP3 p.Ala282Thr Uncertain significance ★ ⚠ same type
ACAP3 p.Ala307Thr Uncertain significance ★ ⚠ same type
ACAP3 p.Ala392Thr Uncertain significance ★ ⚠ same type
ACAP3 p.Ala526Thr Uncertain significance ★ ⚠ same type
ACAP3 p.Ala596Val Uncertain significance ★ ⚠ same type
ACAP3 p.Ala598Thr 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/acap3-p-cys40tyr (accessed [today's date]).

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