Is APBA3 p.Arg247Gln (c.740G>A) pathogenic?

APBA3 p.Arg247Gln (c.740G>A) is classified Likely benign in APBA3 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-05-23). AlphaMissense: likely benign (0.066); Ultra-rare (popmax 0.0107%, nfe).

How common is APBA3 p.Arg247Gln (c.740G>A) in the general population?

APBA3 p.Arg247Gln (c.740G>A) is ultra-rare (popmax 0.0107%, nfe) (gnomAD).

What do computational predictors say about APBA3 p.Arg247Gln (c.740G>A)?

AlphaMissense predicts likely benign (score 0.066) — an in-silico prediction, not a clinical call.

APBA3 p.Arg247Gln

c.740G>A · rs749088363 · VCV2563417

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.066 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0107%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.066	likely benign
REVEL	0.087	moderately benign-leaning
SaProt	LLR -4.11	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 2.1	GERP -1.2, phastCons 1
Regional constraint	o/e 1.05	unconstrained · MANE · 9,235 bp · p 0.12 · regional, not allelic
Overall
CADD	17.87	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 0.0107% European (non-Finnish) · 122/1,142,944 alleles

Filtering AF 0.00913% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00855%

Overall 0.00883% 136/1,539,794 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0107%	9,368
East Asian	0.00981%	10,194
South Asian	0.006%	16,656
African / African-American	0.00414%	24,146
Finnishnot grpmax-eligible	0.0034%	29,403

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: APBA3
Protein: p.Arg247Gln
Coding: c.740G>A
MANE Select: NM_004886
dbSNP: rs749088363
Type: single nucleotide variant
Location: chr19:3754217 (GRCh38)
Gene constraint: LOEUF 1.237 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 64.79 · 3 PDB
Residue 247: the pid domain; the 'required for interaction with necab3' region

Full APBA3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

APBA3 p.Arg247Trp Uncertain significance ★ ⚠ same residue
APBA3 p.Ala158Val Uncertain significance ★ ⚠ same type
APBA3 p.Ala202Val Uncertain significance ★ ⚠ same type
APBA3 p.Ala223Val Uncertain significance ★ ⚠ same type
APBA3 p.Ala308Val Uncertain significance ★ ⚠ same type
APBA3 p.Ala317Val Uncertain significance ★ ⚠ same type
APBA3 p.Ala335Thr Uncertain significance ★ ⚠ same type
APBA3 p.Ala335Val 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/apba3-p-arg247gln (accessed [today's date]).

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