Is AP3B2 p.Ser34Pro (c.100T>C) pathogenic?

AP3B2 p.Ser34Pro (c.100T>C) is classified Uncertain significance in AP3B2 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-08-15). AlphaMissense: likely benign (0.3268); Very rare (popmax 0.0021%, amr).

How common is AP3B2 p.Ser34Pro (c.100T>C) in the general population?

AP3B2 p.Ser34Pro (c.100T>C) is very rare (popmax 0.0021%, amr) (gnomAD).

What do computational predictors say about AP3B2 p.Ser34Pro (c.100T>C)?

AlphaMissense predicts likely benign (score 0.3268) — an in-silico prediction, not a clinical call.

AP3B2 p.Ser34Pro

c.100T>C · rs1458171322 · VCV1472156

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.3268 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0021%, amr)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.3268	likely benign
REVEL	0.294	indeterminate
SaProt	LLR -9.48	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 8.7	GERP 1.1, phastCons 1
Regional constraint	o/e 0.50	unconstrained · MANE · 29 kb · p 3.5e-16 · regional, not allelic
Overall
CADD	26.2	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.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0021% Admixed American · 1/47,662 alleles

Filtering AF 0.000566% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000447%

Overall 0.00103% 14/1,358,948 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0021%	47,662
Remaining individualsnot grpmax-eligible	0.00172%	58,236
European (non-Finnish)	0.00106%	94,254

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.Ser34Pro
Coding: c.100T>C
MANE Select: NM_001278512
dbSNP: rs1458171322
Type: single nucleotide variant
Location: chr15:82709607 (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 p.Ser34del Uncertain significance ★ same residue
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

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-ser34pro (accessed [today's date]).

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