Is AP3B2 p.Ser752Ile (c.2255G>T) pathogenic?

AP3B2 p.Ser752Ile (c.2255G>T) is classified Uncertain significance in AP3B2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-07-31). AlphaMissense: likely benign (0.1064); Very rare (popmax 0.000678%, nfe); Associated with Inborn genetic diseases.

What condition is associated with AP3B2 p.Ser752Ile (c.2255G>T)?

AP3B2 p.Ser752Ile (c.2255G>T) is associated with Inborn genetic diseases (ClinVar).

How common is AP3B2 p.Ser752Ile (c.2255G>T) in the general population?

AP3B2 p.Ser752Ile (c.2255G>T) is very rare (popmax 0.000678%, nfe) (gnomAD).

What do computational predictors say about AP3B2 p.Ser752Ile (c.2255G>T)?

AlphaMissense predicts likely benign (score 0.1064) — an in-silico prediction, not a clinical call.

AP3B2 p.Ser752Ile

c.2255G>T · VCV4115209

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1064 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000678%, nfe)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1064	likely benign
REVEL	0.159	moderately benign-leaning
SaProt	LLR -11.23	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.2	GERP 1.6, phastCons 1
Regional constraint	o/e 1.03	unconstrained · MANE · 5,925 bp · p 0.51 · regional, not allelic
Overall
CADD	23.8	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 S733I vs ClinVar S752I) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000678% European (non-Finnish) · 8/1,179,886 alleles

Filtering AF 0.000292% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000211%

Overall 0.000547% 8/1,461,622 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.Ser752Ile
Coding: c.2255G>T
MANE Select: NM_001278512
Type: single nucleotide variant
Location: chr15:82664373 (GRCh38)
Gene constraint: LOEUF 0.52 · pLI 0.22 (gnomAD)
Structure: AlphaFold pLDDT 75.73
Residue 752: 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.Ala710Thr Uncertain significance ★★ ⚠ same condition
AP3B2 p.Ala71Thr Uncertain significance ★★ ⚠ same condition
AP3B2 p.Ala819Val 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-ser752ile (accessed [today's date]).

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