Is AP3B2 p.Pro986Arg (c.2957C>G) pathogenic?

AP3B2 p.Pro986Arg (c.2957C>G) is classified Uncertain significance in AP3B2 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-07-18). AlphaMissense: likely benign (0.2198); Very rare (popmax 6.84e-05%).

How common is AP3B2 p.Pro986Arg (c.2957C>G) in the general population?

AP3B2 p.Pro986Arg (c.2957C>G) is very rare (popmax 6.84e-05%) (gnomAD).

What do computational predictors say about AP3B2 p.Pro986Arg (c.2957C>G)?

AlphaMissense predicts likely benign (score 0.2198) — an in-silico prediction, not a clinical call.

AP3B2 p.Pro986Arg

c.2957C>G · rs2151426949 · VCV1397514

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2198 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 6.84e-05%)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.2198	likely benign
REVEL	0.628	indeterminate
SaProt	LLR -12.71	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL makes no call.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 12	GERP 1.9, phastCons 1
Regional constraint	o/e 1.03	unconstrained · MANE · 5,925 bp · p 0.51 · regional, not allelic
Overall
CADD	25.9	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM P967R vs ClinVar P986R) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 6.84e-05%

Overall 6.84e-05% 1/1,461,640 alleles · very rare

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: AP3B2
Protein: p.Pro986Arg
Coding: c.2957C>G
dbSNP: rs2151426949
Type: single nucleotide variant
Location: chr15:82661884 (GRCh38)

Full AP3B2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

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/ap3b2-p-pro986arg (accessed [today's date]).

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