Is APBA1 p.Asp643Asn (c.1927G>A) pathogenic?

APBA1 p.Asp643Asn (c.1927G>A) is classified Uncertain significance in APBA1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-03-21). AlphaMissense: ambiguous (0.5103); Ultra-rare (popmax 0.0165%, mid).

How common is APBA1 p.Asp643Asn (c.1927G>A) in the general population?

APBA1 p.Asp643Asn (c.1927G>A) is ultra-rare (popmax 0.0165%, mid) (gnomAD).

What do computational predictors say about APBA1 p.Asp643Asn (c.1927G>A)?

AlphaMissense predicts ambiguous (score 0.5103) — an in-silico prediction, not a clinical call.

APBA1 p.Asp643Asn

c.1927G>A · VCV3924192

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5103 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0165%, mid)

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.5103	ambiguous
REVEL	0.251	benign-leaning
SaProt	LLR -12.03	damaging
⇒ SaProt calls this damaging; REVEL does not; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 1.9, phastCons 1
Regional constraint	o/e 0.58	unconstrained · MANE · 6,665 bp · p 6.5e-08 · regional, not allelic
Overall
CADD	29.9	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 0.0165% Middle Eastern · 1/6,062 alleles

Filtering AF 0.000739% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000539%

Overall 0.0013% 19/1,461,864 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0165%	6,062
East Asian	0.00446%	22,443
Remaining individualsnot grpmax-eligible	0.0032%	31,255
European (non-Finnish)	0.00119%	84,286

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: APBA1
Protein: p.Asp643Asn
Coding: c.1927G>A
MANE Select: NM_001163
Type: single nucleotide variant
Location: chr9:69452163 (GRCh38)
Gene constraint: LOEUF 0.978 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 58.85 · 8 PDB
Residue 643: the pid domain

Full APBA1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

APBA1 p.Asn810Ser Uncertain significance ★★ ⚠ same type
APBA1 p.Ala225Val Uncertain significance ★ ⚠ same type
APBA1 p.Ala329Val Uncertain significance ★ ⚠ same type
APBA1 p.Ala345Thr Uncertain significance ★ ⚠ same type
APBA1 p.Ala506Pro Uncertain significance ★ ⚠ same type
APBA1 p.Ala574Val Uncertain significance ★ ⚠ same type
APBA1 p.Arg143Cys Uncertain significance ★ ⚠ same type
APBA1 p.Arg177His 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/apba1-p-asp643asn (accessed [today's date]).

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