Is APBA2 p.Ile229= (c.687C>T) pathogenic?

APBA2 p.Ile229= (c.687C>T) is classified Likely benign in APBA2 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-10-30). Ultra-rare (popmax 0.0234%, nfe); Associated with APBA2-related disorder.

What condition is associated with APBA2 p.Ile229= (c.687C>T)?

APBA2 p.Ile229= (c.687C>T) is associated with APBA2-related disorder (ClinVar).

How common is APBA2 p.Ile229= (c.687C>T) in the general population?

APBA2 p.Ile229= (c.687C>T) is ultra-rare (popmax 0.0234%, nfe) (gnomAD).

APBA2 p.Ile229=

c.687C>T · rs143079268 · VCV3045439

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0234%, nfe)

Conditions

APBA2-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -6.5	GERP -3.1
Overall
CADD	3.961	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0234% European (non-Finnish) · 276/1,179,942 alleles

Filtering AF 0.0211% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0202%

Overall 0.0194% 313/1,613,812 alleles · ultra-rare exomes 280/1,461,600 · genomes 33/152,212 · joint denominator

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	0.0507%	1,973
European (non-Finnish)grpmax	0.0234%	4,275
Middle Eastern	0.0164%	6,084
African / African-American	0.0107%	9,368
Remaining individualsnot grpmax-eligible	0.0096%	10,412
Admixed American	0.00667%	14,995
Finnishnot grpmax-eligible	0.00312%	32,004
East Asian	0.00223%	44,874

Ashkenazi Jewish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Ile229=
Coding: c.687C>T
MANE Select: NM_001353788
dbSNP: rs143079268
Type: single nucleotide variant
Location: chr15:29054571 (GRCh38)
Gene constraint: LOEUF 0.524 · pLI 0.78 (gnomAD)
Structure: AlphaFold pLDDT 59.74
Residue 229: the 'stxbp1-binding' region

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

Disease context

APBA2-related disorder

Similar variants

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
APBA2 p.Gln408= 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-ile229 (accessed [today's date]).

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