Is AP1M2 p.Pro150Leu (c.449C>T) pathogenic?

AP1M2 p.Pro150Leu (c.449C>T) is classified Uncertain significance in AP1M2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-01-02). AlphaMissense: ambiguous (0.5217); Absent from gnomAD v4.1.

How common is AP1M2 p.Pro150Leu (c.449C>T) in the general population?

AP1M2 p.Pro150Leu (c.449C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about AP1M2 p.Pro150Leu (c.449C>T)?

AlphaMissense predicts ambiguous (score 0.5217) — an in-silico prediction, not a clinical call.

AP1M2 p.Pro150Leu

c.449C>T · rs2512511484 · VCV3127472

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5217 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Computational evidence

Protein change
AlphaMissense	0.5217	ambiguous
REVEL	0.432	indeterminate
SaProt	LLR -12.72	damaging
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 1.7, phastCons 1
Regional constraint	o/e 0.90	unconstrained · MANE · 14 kb · p 0.022 · regional, not allelic
Overall
CADD	31.0	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: AP1M2
Protein: p.Pro150Leu
Coding: c.449C>T
MANE Select: NM_005498
dbSNP: rs2512511484
Type: single nucleotide variant
Location: chr19:10581584 (GRCh38)
Gene constraint: LOEUF 1.073 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 93.03

Full AP1M2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

AP1M2 p.Ala156Gly Uncertain significance ★ ⚠ same type
AP1M2 p.Ala156Thr Uncertain significance ★ ⚠ same type
AP1M2 p.Ala3Val Uncertain significance ★ ⚠ same type
AP1M2 p.Ala405Thr Uncertain significance ★ ⚠ same type
AP1M2 p.Arg104Gln Uncertain significance ★ ⚠ same type
AP1M2 p.Arg148Gln Uncertain significance ★ ⚠ same type
AP1M2 p.Arg148Trp Uncertain significance ★ ⚠ same type
AP1M2 p.Arg19Cys 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/ap1m2-p-pro150leu (accessed [today's date]).

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