Is AP2M1 p.Arg40Gln (c.119G>A) pathogenic?

AP2M1 p.Arg40Gln (c.119G>A) is classified Uncertain significance in AP2M1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-12-06). AlphaMissense: likely pathogenic (0.9373); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with AP2M1 p.Arg40Gln (c.119G>A)?

AP2M1 p.Arg40Gln (c.119G>A) is associated with Inborn genetic diseases (ClinVar).

How common is AP2M1 p.Arg40Gln (c.119G>A) in the general population?

AP2M1 p.Arg40Gln (c.119G>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about AP2M1 p.Arg40Gln (c.119G>A)?

AlphaMissense predicts likely pathogenic (score 0.9373) — an in-silico prediction, not a clinical call.

AP2M1 p.Arg40Gln

c.119G>A · VCV3403860

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9373 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.9373	likely pathogenic
REVEL	0.285	benign-leaning
SaProt	LLR -8.28	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 1.6, phastCons 1
Regional constraint	o/e 0.35	constrained · MANE · 4,753 bp · p 1.5e-32 · regional, not allelic
Overall
CADD	33.0	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

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.Arg40Gln
Coding: c.119G>A
MANE Select: NM_004068
Type: single nucleotide variant
Location: chr3:184178901 (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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

AP2M1 p.Arg40Trp Uncertain significance ★★ ⚠ same residue
AP2M1 p.Ala28Thr Uncertain significance ★★ ⚠ same condition
AP2M1 p.Arg169His Uncertain significance ★★ ⚠ same condition
AP2M1 p.Ser97Gly Uncertain significance ★★ ⚠ same condition
AP2M1 p.Val352Met Uncertain significance ★★ ⚠ same condition
AP2M1 p.Ala194Asp Uncertain significance ★ ⚠ same condition
AP2M1 p.Ala67Thr Conflicting classifications of pathogenicity ★ ⚠ same condition
AP2M1 p.Arg162Gln Uncertain significance ★ ⚠ same condition

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-arg40gln (accessed [today's date]).

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