Is APBA2 p.Gly603= (c.1809C>T) pathogenic?

APBA2 p.Gly603= (c.1809C>T) is classified Benign in APBA2 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-05-01). Common (popmax 18.4%, afr) — too common for a highly-penetrant pathogenic allele; Associated with APBA2-related disorder.

What condition is associated with APBA2 p.Gly603= (c.1809C>T)?

APBA2 p.Gly603= (c.1809C>T) is associated with APBA2-related disorder (ClinVar).

APBA2 p.Gly603=

Q: How common is APBA2 p.Gly603= (c.1809C>T) in the general population?

APBA2 p.Gly603= (c.1809C>T) is common (popmax 18.4%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.1809C>T · rs8032178 · VCV3056994

Benign No assertion criteria

Classification

Benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Common

common (popmax 18.4%, afr) — too common for a highly-penetrant pathogenic allele

Conditions

APBA2-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -20	GERP -3.7
Overall
CADD	0.079	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 18.4% African / African-American · 13,814/74,968 alleles

Filtering AF 18.2% ClinGen BA1/BS1 input FAF95, joint · FAF99 18.1%

Overall 0.961% 15,508/1,612,946 alleles · common

Ancestry group	Frequency	1 in
African / African-Americangrpmax	18.4%	5
Remaining individualsnot grpmax-eligible	1.14%	88
Admixed American	1.04%	96
Middle Eastern	0.594%	168
South Asian	0.0417%	2,397
East Asian	0.0334%	2,990
European (non-Finnish)	0.0225%	4,453
Finnishnot grpmax-eligible	0.00159%	62,968

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: APBA2
Protein: p.Gly603=
Coding: c.1809C>T
MANE Select: NM_001353788
dbSNP: rs8032178
Type: single nucleotide variant
Location: chr15:29106711 (GRCh38)
Gene constraint: LOEUF 0.524 · pLI 0.78 (gnomAD)
Structure: AlphaFold pLDDT 59.74
Residue 603: the pdz 1 domain

Full APBA2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

APBA2-related disorder

Similar variants

APBA2 p.Gly603Ala Uncertain significance ★ ⚠ same residue
APBA2 c.1070-9C>T Likely benign same condition
APBA2 c.952-3825C>T Likely benign same condition
APBA2 c.*7C>T Likely benign same condition
APBA2 p.Arg52Gln Benign same condition
APBA2 p.Asn704= Likely benign same condition
APBA2 p.Asn722Ser Likely benign same condition
APBA2 p.Asp162= Likely benign 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/apba2-p-gly603 (accessed [today's date]).

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