Is ACAP1 p.Val407Glu (c.1220T>A) pathogenic?

ACAP1 p.Val407Glu (c.1220T>A) is classified Uncertain significance in ACAP1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-30). AlphaMissense: ambiguous (0.451); Very rare (popmax 0.00167%, amr).

How common is ACAP1 p.Val407Glu (c.1220T>A) in the general population?

ACAP1 p.Val407Glu (c.1220T>A) is very rare (popmax 0.00167%, amr) (gnomAD).

What do computational predictors say about ACAP1 p.Val407Glu (c.1220T>A)?

AlphaMissense predicts ambiguous (score 0.451) — an in-silico prediction, not a clinical call.

ACAP1 p.Val407Glu

c.1220T>A · rs753865344 · VCV3135473

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.451 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00167%, amr)

Computational evidence

Protein change
AlphaMissense	0.451	ambiguous
REVEL	0.31	indeterminate
SaProt	LLR -11.56	damaging
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6.2	GERP 2.5, phastCons 1
Regional constraint	o/e 0.81	unconstrained · MANE · 10 kb · p 1e-05 · regional, not allelic
Overall
CADD	25.0	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 0.00167% Admixed American · 1/59,970 alleles

Overall 0.000657% 1/152,158 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.Val407Glu
Coding: c.1220T>A
MANE Select: NM_014716
dbSNP: rs753865344
Type: single nucleotide variant
Location: chr17:7347119 (GRCh38)
Gene constraint: LOEUF 0.579 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 84.92 · 7 PDB
Residue 407: the arf-gap domain; an α-helix; the 'required for interaction with gulp1' region

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

Similar variants

ACAP1 p.Val407Ala Uncertain significance ★★ ⚠ same residue
ACAP1 p.Val407Met Uncertain significance ★ ⚠ same residue
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

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-val407glu (accessed [today's date]).

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