Is AP3B2 p.Ser352Arg (c.1054A>C) pathogenic?

AP3B2 p.Ser352Arg (c.1054A>C) is classified Uncertain significance in AP3B2 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-08-04). AlphaMissense: ambiguous (0.5077); Very rare (popmax 0.000355%, nfe).

How common is AP3B2 p.Ser352Arg (c.1054A>C) in the general population?

AP3B2 p.Ser352Arg (c.1054A>C) is very rare (popmax 0.000355%, nfe) (gnomAD).

What do computational predictors say about AP3B2 p.Ser352Arg (c.1054A>C)?

AlphaMissense predicts ambiguous (score 0.5077) — an in-silico prediction, not a clinical call.

AP3B2 p.Ser352Arg

c.1054A>C · rs1433929710 · VCV1442482

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5077 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000355%, nfe)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.5077	ambiguous
REVEL	0.1	moderately benign-leaning
SaProt	LLR 3.66	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	Δ0.71	donor gain · deltas
Pangolin	Δ0.23	gain · loss 0.10 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 4.8	GERP 0.66, phastCons 1
Regional constraint	o/e 0.68	unconstrained · MANE · 15 kb · p 1.1e-11 · regional, not allelic
Overall
CADD	34.0	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 0.000355% European (non-Finnish) · 4/1,126,436 alleles

Filtering AF 8.3e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 5.6e-05%

Overall 0.000267% 4/1,497,872 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.Ser352Arg
Coding: c.1054A>C
MANE Select: NM_001278512
dbSNP: rs1433929710
Type: single nucleotide variant
Location: chr15:82680473 (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-ser352arg (accessed [today's date]).

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