Is AP2M1 p.Thr330= (c.990A>T) pathogenic?

AP2M1 p.Thr330= (c.990A>T) is classified Likely benign in AP2M1 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-12-11). Absent from gnomAD v4.1.

How common is AP2M1 p.Thr330= (c.990A>T) in the general population?

AP2M1 p.Thr330= (c.990A>T) is absent from gnomAD v4.1 (gnomAD).

AP2M1 p.Thr330=

c.990A>T · rs2473726178 · VCV2806372

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.14	GERP -3.7, phastCons 0.008
Overall
CADD	8.03	PHRED · no single calibrated threshold — expert panels disagree

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.Thr330=
Coding: c.990A>T
MANE Select: NM_004068
dbSNP: rs2473726178
Type: single nucleotide variant
Location: chr3:184182177 (GRCh38)
Gene constraint: LOEUF 0.182 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 89.44 · 3 PDB
Residue 330: the mhd domain; a β-strand

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

Similar variants

AP2M1 p.Thr330Arg Uncertain significance ★ ⚠ same residue
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

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-thr330 (accessed [today's date]).

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