Is AP1S2 p.Ala40Val (c.119C>T) pathogenic?

AP1S2 p.Ala40Val (c.119C>T) is classified Uncertain significance in AP1S2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-02-19). AlphaMissense: likely benign (0.2923); Absent from gnomAD v4.1.

How common is AP1S2 p.Ala40Val (c.119C>T) in the general population?

AP1S2 p.Ala40Val (c.119C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about AP1S2 p.Ala40Val (c.119C>T)?

AlphaMissense predicts likely benign (score 0.2923) — an in-silico prediction, not a clinical call.

AP1S2 p.Ala40Val

c.119C>T · rs2519929560 · VCV1722221

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2923 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.2923	likely benign
REVEL	0.489	indeterminate
SaProt	LLR -10.06	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 1.9, phastCons 1
Regional constraint	o/e 0.25	constrained · MANE · 6,547 bp · p 4.2e-08 · regional, not allelic
Overall
CADD	25.3	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: AP1S2
Protein: p.Ala40Val
Coding: c.119C>T
MANE Select: NM_001272071
dbSNP: rs2519929560
Type: single nucleotide variant
Location: chrX:15852406 (GRCh38)
Structure: AlphaFold pLDDT 94.36

Full AP1S2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

AP1S2 c.-1+1G>A Pathogenic/Likely pathogenic ★★ same type
AP1S2 p.Arg52Ter Pathogenic ★★ same type
AP1S2 p.Gln123Ter Pathogenic ★★ same type
AP1S2 p.Asn129Thr Uncertain significance ★★ ⚠ same type
AP1S2 p.Gly158Arg Uncertain significance ★★ ⚠ same type
AP1S2 p.Ile134Thr Uncertain significance ★★ ⚠ same type
AP1S2 p.Ile82Val Uncertain significance ★★ ⚠ same type
AP1S2 p.Leu54Val 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/ap1s2-p-ala40val (accessed [today's date]).

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