Is ACAP3 p.Gln301Arg (c.902A>G) pathogenic?

ACAP3 p.Gln301Arg (c.902A>G) is classified Uncertain significance in ACAP3 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-12). AlphaMissense: ambiguous (0.3584); Ultra-rare (popmax 0.0157%, eas).

How common is ACAP3 p.Gln301Arg (c.902A>G) in the general population?

ACAP3 p.Gln301Arg (c.902A>G) is ultra-rare (popmax 0.0157%, eas) (gnomAD).

What do computational predictors say about ACAP3 p.Gln301Arg (c.902A>G)?

AlphaMissense predicts ambiguous (score 0.3584) — an in-silico prediction, not a clinical call.

ACAP3 p.Gln301Arg

c.902A>G · rs575628799 · VCV3135726

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3584 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0157%, eas)

Computational evidence

Protein change
AlphaMissense	0.3584	ambiguous
REVEL	0.434	indeterminate
SaProt	LLR -9.94	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6.1	GERP 2.6, phastCons 1
Regional constraint	o/e 1.03	unconstrained · MANE · 14 kb · p 0.33 · regional, not allelic
Overall
CADD	26.7	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 0.0157% East Asian · 7/44,716 alleles

Filtering AF 0.00728% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00516%

Overall 0.000935% 15/1,603,476 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0157%	6,388
Remaining individualsnot grpmax-eligible	0.00968%	10,326
European (non-Finnish)	0.00017%	587,613

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.Gln301Arg
Coding: c.902A>G
MANE Select: NM_030649
dbSNP: rs575628799
Type: single nucleotide variant
Location: chr1:1298383 (GRCh38)
Gene constraint: LOEUF 0.816 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 76.31
Residue 301: the ph domain

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-gln301arg (accessed [today's date]).

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