Is APBB3 p.Arg323Gln (c.968G>A) pathogenic?

APBB3 p.Arg323Gln (c.968G>A) is classified Likely benign in APBB3 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-10-12). AlphaMissense: likely benign (0.0607); Ultra-rare (popmax 0.0999%, afr).

How common is APBB3 p.Arg323Gln (c.968G>A) in the general population?

APBB3 p.Arg323Gln (c.968G>A) is ultra-rare (popmax 0.0999%, afr) (gnomAD).

What do computational predictors say about APBB3 p.Arg323Gln (c.968G>A)?

AlphaMissense predicts likely benign (score 0.0607) — an in-silico prediction, not a clinical call.

APBB3 p.Arg323Gln

c.968G>A · rs147781373 · VCV2364526

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0607 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0999%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0607	likely benign
REVEL	0.042	moderately benign-leaning
SaProt	LLR -4.25	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 -7.9	GERP -3.4
Regional constraint	o/e 0.84	unconstrained · MANE · 3,819 bp · p 0.00036 · regional, not allelic
Overall
CADD	0.582	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 0.0999% African / African-American · 75/75,042 alleles

Filtering AF 0.0817% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.075%

Overall 0.00644% 104/1,614,208 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0999%	1,001
Remaining individualsnot grpmax-eligible	0.0032%	31,256
South Asian	0.0022%	45,544
European (non-Finnish)	0.00203%	49,168
Finnishnot grpmax-eligible	0.00156%	64,034

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: APBB3
Protein: p.Arg323Gln
Coding: c.968G>A
MANE Select: NM_133173
dbSNP: rs147781373
Type: single nucleotide variant
Location: chr5:140560703 (GRCh38)
Gene constraint: LOEUF 0.973 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 64.76 · 2 PDB
Residue 323: the pid 2 domain

Full APBB3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

APBB3 p.Arg323Trp Uncertain significance ★ ⚠ same residue
APBB3 p.Ala135Gly Uncertain significance ★ ⚠ same type
APBB3 p.Ala151Val Uncertain significance ★ ⚠ same type
APBB3 p.Ala163Thr Uncertain significance ★ ⚠ same type
APBB3 p.Ala288Thr Uncertain significance ★ ⚠ same type
APBB3 p.Ala313Val Uncertain significance ★ ⚠ same type
APBB3 p.Ala475Asp Uncertain significance ★ ⚠ same type
APBB3 p.Arg122Cys 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/apbb3-p-arg323gln (accessed [today's date]).

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