Is AP3M1 p.Ser286Cys (c.856A>T) pathogenic?

AP3M1 p.Ser286Cys (c.856A>T) is classified Uncertain significance in AP3M1 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-06-24). AlphaMissense: likely benign (0.0751); Very rare (popmax 0.00267%, afr).

How common is AP3M1 p.Ser286Cys (c.856A>T) in the general population?

AP3M1 p.Ser286Cys (c.856A>T) is very rare (popmax 0.00267%, afr) (gnomAD).

What do computational predictors say about AP3M1 p.Ser286Cys (c.856A>T)?

AlphaMissense predicts likely benign (score 0.0751) — an in-silico prediction, not a clinical call.

AP3M1 p.Ser286Cys

c.856A>T · rs1300004917 · VCV2296401

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0751 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00267%, afr)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0751	likely benign
REVEL	0.129	moderately benign-leaning
SaProt	LLR -10.25	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	Δ0.31	acceptor gain · deltas
Constraint at this position
Conservation	phyloP 7.9	GERP 1.7, phastCons 1
Regional constraint	o/e 0.82	unconstrained · MANE · 15 kb · p 3e-05 · 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

Grpmax group 0.00267% African / African-American · 2/74,926 alleles

Filtering AF 0.000443% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000166%

Overall 0.000186% 3/1,614,092 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00267%	37,463
Remaining individualsnot grpmax-eligible	0.0016%	62,490

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: AP3M1
Protein: p.Ser286Cys
Coding: c.856A>T
MANE Select: NM_012095
dbSNP: rs1300004917
Type: single nucleotide variant
Location: chr10:74126303 (GRCh38)
Gene constraint: LOEUF 0.823 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 92.18 · 5 PDB
Residue 286: the mhd domain

Full AP3M1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

AP3M1 p.Ala40Val Uncertain significance ★ ⚠ same type
AP3M1 p.Arg168Cys Uncertain significance ★ ⚠ same type
AP3M1 p.Arg169Gln Uncertain significance ★ ⚠ same type
AP3M1 p.Arg241Cys Uncertain significance ★ ⚠ same type
AP3M1 p.Arg241His Uncertain significance ★ ⚠ same type
AP3M1 p.Arg391Cys Uncertain significance ★ ⚠ same type
AP3M1 p.Arg61Gln Uncertain significance ★ ⚠ same type
AP3M1 p.Asn145Ser 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/ap3m1-p-ser286cys (accessed [today's date]).

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