Is ACAP3 p.Ser369Arg (c.1107C>A) pathogenic?

ACAP3 p.Ser369Arg (c.1107C>A) is classified Uncertain significance in ACAP3 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-11-29). AlphaMissense: likely pathogenic (0.6091); Ultra-rare (popmax 0.0333%, amr).

How common is ACAP3 p.Ser369Arg (c.1107C>A) in the general population?

ACAP3 p.Ser369Arg (c.1107C>A) is ultra-rare (popmax 0.0333%, amr) (gnomAD).

What do computational predictors say about ACAP3 p.Ser369Arg (c.1107C>A)?

AlphaMissense predicts likely pathogenic (score 0.6091) — an in-silico prediction, not a clinical call.

ACAP3 p.Ser369Arg

c.1107C>A · rs558870678 · VCV3135637

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6091 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0333%, amr)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.6091	likely pathogenic
REVEL	0.113	moderately benign-leaning
SaProt	LLR -4.68	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.8	GERP 1.3, phastCons 1
Regional constraint	o/e 1.03	unconstrained · MANE · 14 kb · p 0.33 · regional, not allelic
Overall
CADD	22.0	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 0.0333% Admixed American · 20/59,994 alleles

Filtering AF 0.0221% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0184%

Overall 0.00149% 24/1,611,760 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0333%	3,000
Remaining individualsnot grpmax-eligible	0.0048%	20,814
European (non-Finnish)	8.48e-05%	1,179,332

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.Ser369Arg
Coding: c.1107C>A
MANE Select: NM_030649
dbSNP: rs558870678
Type: single nucleotide variant
Location: chr1:1297843 (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-ser369arg (accessed [today's date]).

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