Is AP2M1 p.Ile96Val (c.286A>G) pathogenic?

AP2M1 p.Ile96Val (c.286A>G) is classified Uncertain significance in AP2M1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-08-10). AlphaMissense: likely benign (0.0848); Absent from gnomAD v4.1.

How common is AP2M1 p.Ile96Val (c.286A>G) in the general population?

AP2M1 p.Ile96Val (c.286A>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about AP2M1 p.Ile96Val (c.286A>G)?

AlphaMissense predicts likely benign (score 0.0848) — an in-silico prediction, not a clinical call.

AP2M1 p.Ile96Val

c.286A>G · rs2473719648 · VCV2822611

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0848 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0848	likely benign
REVEL	0.184	benign-leaning
SaProt	LLR -4.31	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	Δ0.91	donor gain · deltas
Pangolin	Δ0.40	gain · loss 0.00 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 9.4	GERP 1.9, phastCons 1
Regional constraint	o/e 0.35	constrained · MANE · 4,753 bp · p 1.5e-32 · regional, not allelic
Overall
CADD	29.7	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

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: AP2M1
Protein: p.Ile96Val
Coding: c.286A>G
MANE Select: NM_004068
dbSNP: rs2473719648
Type: single nucleotide variant
Location: chr3:184179068 (GRCh38)
Gene constraint: LOEUF 0.182 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 89.44 · 3 PDB

Full AP2M1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

AP2M1 p.Arg170Trp Pathogenic/Likely pathogenic ★★ same type
AP2M1 p.Ala28Thr Uncertain significance ★★ ⚠ same type
AP2M1 p.Arg169His Uncertain significance ★★ ⚠ same type
AP2M1 p.Arg199Gln Uncertain significance ★★ ⚠ same type
AP2M1 p.Arg40Trp Uncertain significance ★★ ⚠ same type
AP2M1 p.Arg44His Uncertain significance ★★ ⚠ same type
AP2M1 p.Cys246Arg Uncertain significance ★★ ⚠ same type
AP2M1 p.Cys86Tyr 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/ap2m1-p-ile96val (accessed [today's date]).

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