Is AP1S2 p.Glu155Val (c.464A>T) pathogenic?

AP1S2 p.Glu155Val (c.464A>T) is classified Uncertain significance in AP1S2 (ClinVar, Single submitter, 2 submitters; last evaluated 2025-06-11). AlphaMissense: likely pathogenic (0.648); Absent from gnomAD v4.1.

How common is AP1S2 p.Glu155Val (c.464A>T) in the general population?

AP1S2 p.Glu155Val (c.464A>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about AP1S2 p.Glu155Val (c.464A>T)?

AlphaMissense predicts likely pathogenic (score 0.648) — an in-silico prediction, not a clinical call.

AP1S2 p.Glu155Val

c.464A>T · VCV4481397

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.648 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.648	likely pathogenic
REVEL	0.218	benign-leaning
SaProt	LLR -10.52	damaging
⇒ AlphaMissense and SaProt call this damaging; REVEL does not.
Splicing
SpliceAI	Δ0.50	acceptor loss · deltas
Pangolin	Δ0.23	loss · gain 0.00 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 7.9	GERP 1.8, phastCons 1
Regional constraint	o/e 0.58	unconstrained · MANE · 18 kb · p 0.042 · regional, not allelic
Overall
CADD	22.4	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM E152V vs ClinVar E155V) — verify the residue.

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.Glu155Val
Coding: c.464A>T
MANE Select: NM_001272071
Type: single nucleotide variant
Location: chrX:15827344 (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-glu155val (accessed [today's date]).

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