Is AP3M2 p.Pro352Ser (c.1054C>T) pathogenic?

AP3M2 p.Pro352Ser (c.1054C>T) is classified Uncertain significance in AP3M2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-13). AlphaMissense: likely pathogenic (0.8196); Absent from gnomAD v4.1.

How common is AP3M2 p.Pro352Ser (c.1054C>T) in the general population?

AP3M2 p.Pro352Ser (c.1054C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about AP3M2 p.Pro352Ser (c.1054C>T)?

AlphaMissense predicts likely pathogenic (score 0.8196) — an in-silico prediction, not a clinical call.

AP3M2 p.Pro352Ser

c.1054C>T · VCV4115541

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8196 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.8196	likely pathogenic
REVEL	0.264	benign-leaning
SaProt	LLR -11.44	damaging
⇒ AlphaMissense and SaProt call this damaging; REVEL does not.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 7.7	GERP 1.9, phastCons 1
Regional constraint	o/e 0.83	unconstrained · MANE · 6,645 bp · p 0.0045 · regional, not allelic
Overall
CADD	27.2	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: AP3M2
Protein: p.Pro352Ser
Coding: c.1054C>T
MANE Select: NM_006803
Type: single nucleotide variant
Location: chr8:42167708 (GRCh38)
Gene constraint: LOEUF 0.858 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 93.07
Residue 352: the mhd domain

Full AP3M2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

AP3M2 p.Ala35Val Uncertain significance ★ ⚠ same type
AP3M2 p.Arg168Gln Uncertain significance ★ ⚠ same type
AP3M2 p.Arg246His Uncertain significance ★ ⚠ same type
AP3M2 p.Arg258Cys Uncertain significance ★ ⚠ same type
AP3M2 p.Arg283Gln Uncertain significance ★ ⚠ same type
AP3M2 p.Arg283Pro Uncertain significance ★ ⚠ same type
AP3M2 p.Arg283Trp Uncertain significance ★ ⚠ same type
AP3M2 p.Arg290Cys 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/ap3m2-p-pro352ser (accessed [today's date]).

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