Is AP3B2 p.Ala710Thr (c.2128G>A) pathogenic?

AP3B2 p.Ala710Thr (c.2128G>A) is classified Uncertain significance in AP3B2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-04-09). AlphaMissense: likely benign (0.2199); Very rare (popmax 0.0068%, eas); Associated with Inborn genetic diseases.

What condition is associated with AP3B2 p.Ala710Thr (c.2128G>A)?

AP3B2 p.Ala710Thr (c.2128G>A) is associated with Inborn genetic diseases (ClinVar).

How common is AP3B2 p.Ala710Thr (c.2128G>A) in the general population?

AP3B2 p.Ala710Thr (c.2128G>A) is very rare (popmax 0.0068%, eas) (gnomAD).

What do computational predictors say about AP3B2 p.Ala710Thr (c.2128G>A)?

AlphaMissense predicts likely benign (score 0.2199) — an in-silico prediction, not a clinical call.

AP3B2 p.Ala710Thr

c.2128G>A · rs765669791 · VCV1960294

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.2199 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0068%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.2199	likely benign
REVEL	0.101	moderately benign-leaning
SaProt	LLR -6.59	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 1.6, phastCons 1
Regional constraint	o/e 1.03	unconstrained · MANE · 5,925 bp · p 0.51 · regional, not allelic
Overall
CADD	26.6	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM A691T vs ClinVar A710T) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0068% East Asian · 3/44,106 alleles

Filtering AF 0.0018% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0009%

Overall 0.00113% 18/1,590,744 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0068%	14,702
South Asian	0.00229%	43,685
Admixed American	0.00176%	56,812
Remaining individualsnot grpmax-eligible	0.00162%	61,596
African / African-American	0.00134%	74,582
European (non-Finnish)	0.000856%	116,780

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.Ala710Thr
Coding: c.2128G>A
MANE Select: NM_001278512
dbSNP: rs765669791
Type: single nucleotide variant
Location: chr15:82664844 (GRCh38)
Gene constraint: LOEUF 0.52 · pLI 0.22 (gnomAD)
Structure: AlphaFold pLDDT 75.73
Residue 710: the 'disordered' region

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

AP3B2 c.2834-3C>A Uncertain significance ★★ same condition
AP3B2 p.Ala1076Pro Uncertain significance ★★ ⚠ same condition
AP3B2 p.Ala1098Asp Uncertain significance ★★ ⚠ same condition
AP3B2 p.Ala4Val Uncertain significance ★★ ⚠ same condition
AP3B2 p.Ala633Val Uncertain significance ★★ ⚠ same condition
AP3B2 p.Ala71Thr Uncertain significance ★★ ⚠ same condition
AP3B2 p.Ala819Val Uncertain significance ★★ ⚠ same condition
AP3B2 p.Arg1025Trp Uncertain significance ★★ ⚠ same condition

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-ala710thr (accessed [today's date]).

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