Is ACAP3 p.Val27Leu (c.79G>T) pathogenic?

ACAP3 p.Val27Leu (c.79G>T) is classified Uncertain significance in ACAP3 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-04-04). AlphaMissense: ambiguous (0.4775); Ultra-rare (popmax 0.0378%, nfe).

How common is ACAP3 p.Val27Leu (c.79G>T) in the general population?

ACAP3 p.Val27Leu (c.79G>T) is ultra-rare (popmax 0.0378%, nfe) (gnomAD).

What do computational predictors say about ACAP3 p.Val27Leu (c.79G>T)?

AlphaMissense predicts ambiguous (score 0.4775) — an in-silico prediction, not a clinical call.

ACAP3 p.Val27Leu

c.79G>T · VCV3261140

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4775 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0378%, nfe)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.4775	ambiguous
REVEL	0.036	moderately benign-leaning
SaProt	LLR -6.07	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.7	GERP -0.76, phastCons 1
Regional constraint	o/e 1.03	unconstrained · MANE · 14 kb · p 0.33 · regional, not allelic
Overall
CADD	23.1	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 0.0378% European (non-Finnish) · 433/1,146,902 alleles

Filtering AF 0.0348% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0336%

Overall 0.029% 449/1,550,634 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0378%	2,649
Remaining individualsnot grpmax-eligible	0.0216%	4,621
African / African-American	0.00274%	36,526
Admixed American	0.00196%	50,986

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.Val27Leu
Coding: c.79G>T
MANE Select: NM_030649
Type: single nucleotide variant
Location: chr1:1304112 (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-val27leu (accessed [today's date]).

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