Is ACAP1 p.Leu5Val (c.13C>G) pathogenic?

ACAP1 p.Leu5Val (c.13C>G) is classified Uncertain significance in ACAP1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-08-14). AlphaMissense: likely benign (0.1627); Very rare (popmax 0.00017%, nfe).

How common is ACAP1 p.Leu5Val (c.13C>G) in the general population?

ACAP1 p.Leu5Val (c.13C>G) is very rare (popmax 0.00017%, nfe) (gnomAD).

What do computational predictors say about ACAP1 p.Leu5Val (c.13C>G)?

AlphaMissense predicts likely benign (score 0.1627) — an in-silico prediction, not a clinical call.

ACAP1 p.Leu5Val

c.13C>G · rs374103329 · VCV2617909

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1627 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00017%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1627	likely benign
REVEL	0.147	moderately benign-leaning
SaProt	LLR -5.51	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 1.1	GERP -0.043, phastCons 1
Regional constraint	o/e 0.81	unconstrained · MANE · 10 kb · p 1e-05 · regional, not allelic
Overall
CADD	19.5	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 0.00017% European (non-Finnish) · 2/1,179,890 alleles

Filtering AF 2.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000137% 2/1,461,702 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: ACAP1
Protein: p.Leu5Val
Coding: c.13C>G
MANE Select: NM_014716
dbSNP: rs374103329
Type: single nucleotide variant
Location: chr17:7336747 (GRCh38)
Gene constraint: LOEUF 0.579 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 84.92 · 7 PDB
Residue 5: the bar domain; the 'required for formation of endosomal tubules when overexpressed with pip5k1c' region

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-leu5val (accessed [today's date]).

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