Is AP3B2 p.Ile430Val (c.1288A>G) pathogenic?

AP3B2 p.Ile430Val (c.1288A>G) is classified Uncertain significance in AP3B2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-06-02). AlphaMissense: ambiguous (0.5062); Very rare (popmax 0.00153%, nfe).

How common is AP3B2 p.Ile430Val (c.1288A>G) in the general population?

AP3B2 p.Ile430Val (c.1288A>G) is very rare (popmax 0.00153%, nfe) (gnomAD).

What do computational predictors say about AP3B2 p.Ile430Val (c.1288A>G)?

AlphaMissense predicts ambiguous (score 0.5062) — an in-silico prediction, not a clinical call.

AP3B2 p.Ile430Val

c.1288A>G · rs1310995941 · VCV2781609

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5062 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00153%, nfe)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.5062	ambiguous
REVEL	0.201	benign-leaning
SaProt	LLR -7.70	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5	GERP 0.89, phastCons 1
Regional constraint	o/e 0.68	unconstrained · MANE · 15 kb · p 1.1e-11 · regional, not allelic
Overall
CADD	25.1	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 0.00153% European (non-Finnish) · 18/1,179,054 alleles

Filtering AF 0.000954% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000787%

Overall 0.00123% 18/1,460,180 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.Ile430Val
Coding: c.1288A>G
MANE Select: NM_001278512
dbSNP: rs1310995941
Type: single nucleotide variant
Location: chr15:82677761 (GRCh38)
Gene constraint: LOEUF 0.52 · pLI 0.22 (gnomAD)
Structure: AlphaFold pLDDT 75.73

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

Similar variants

AP3B2 c.114-1G>A Likely pathogenic ★★ same type
AP3B2 p.Arg977Ter Pathogenic ★★ same type
AP3B2 p.Gln839Ter Pathogenic/Likely pathogenic ★★ same type
AP3B2 c.1110+3G>C Uncertain significance ★★ same type
AP3B2 c.1853-5C>A Uncertain significance ★★ same type
AP3B2 c.2834-3C>A Uncertain significance ★★ same type
AP3B2 p.Ala1076Pro Uncertain significance ★★ ⚠ same type
AP3B2 p.Ala1098Asp 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/ap3b2-p-ile430val (accessed [today's date]).

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