Is ACAP1 p.Val404Leu (c.1210G>C) pathogenic?

ACAP1 p.Val404Leu (c.1210G>C) is classified Uncertain significance in ACAP1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-30). AlphaMissense: likely benign (0.0873); Ultra-rare (popmax 0.0946%, afr).

How common is ACAP1 p.Val404Leu (c.1210G>C) in the general population?

ACAP1 p.Val404Leu (c.1210G>C) is ultra-rare (popmax 0.0946%, afr) (gnomAD).

What do computational predictors say about ACAP1 p.Val404Leu (c.1210G>C)?

AlphaMissense predicts likely benign (score 0.0873) — an in-silico prediction, not a clinical call.

ACAP1 p.Val404Leu

c.1210G>C · rs145239336 · VCV2590105

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0873 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0946%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0873	likely benign
REVEL	0.065	moderately benign-leaning
SaProt	LLR -6.17	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.7	GERP 1.3, phastCons 0.12
Regional constraint	o/e 0.81	unconstrained · MANE · 10 kb · p 1e-05 · regional, not allelic
Overall
CADD	11.93	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.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0946% African / African-American · 71/75,062 alleles

Filtering AF 0.0769% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0704%

Overall 0.00477% 77/1,613,758 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0946%	1,057
Middle Eastern	0.0165%	6,046
Remaining individualsnot grpmax-eligible	0.0048%	20,829
South Asian	0.0022%	45,531

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: ACAP1
Protein: p.Val404Leu
Coding: c.1210G>C
MANE Select: NM_014716
dbSNP: rs145239336
Type: single nucleotide variant
Location: chr17:7347109 (GRCh38)
Gene constraint: LOEUF 0.579 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 84.92 · 7 PDB

Full ACAP1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ACAP1 p.Val407Ala Uncertain significance ★★ ⚠ same type
ACAP1 p.Ala137Thr Uncertain significance ★ ⚠ same type
ACAP1 p.Ala418Asp Uncertain significance ★ ⚠ same type
ACAP1 p.Ala54Thr Uncertain significance ★ ⚠ same type
ACAP1 p.Ala58Asp Uncertain significance ★ ⚠ same type
ACAP1 p.Ala596Thr Uncertain significance ★ ⚠ same type
ACAP1 p.Ala636Glu Uncertain significance ★ ⚠ same type
ACAP1 p.Ala636Val 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/acap1-p-val404leu (accessed [today's date]).

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