Is APBA2 p.Ile614Val (c.1840A>G) pathogenic?

APBA2 p.Ile614Val (c.1840A>G) is classified Uncertain significance in APBA2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-06-10). AlphaMissense: likely benign (0.1836); Very rare (popmax 0.00446%, eas).

How common is APBA2 p.Ile614Val (c.1840A>G) in the general population?

APBA2 p.Ile614Val (c.1840A>G) is very rare (popmax 0.00446%, eas) (gnomAD).

What do computational predictors say about APBA2 p.Ile614Val (c.1840A>G)?

AlphaMissense predicts likely benign (score 0.1836) — an in-silico prediction, not a clinical call.

APBA2 p.Ile614Val

c.1840A>G · VCV3924436

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1836 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00446%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1836	likely benign
REVEL	0.207	benign-leaning
SaProt	LLR -8.66	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 8	GERP 1.9, phastCons 1
Overall
CADD	23.9	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00446% East Asian · 2/44,870 alleles

Filtering AF 0.000739% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000276%

Overall 0.00031% 5/1,612,954 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00446%	22,435
African / African-American	0.00133%	74,918
European (non-Finnish)	0.000169%	590,009

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.Ile614Val
Coding: c.1840A>G
MANE Select: NM_001353788
Type: single nucleotide variant
Location: chr15:29106742 (GRCh38)
Gene constraint: LOEUF 0.524 · pLI 0.78 (gnomAD)
Structure: AlphaFold pLDDT 59.74
Residue 614: the pdz 1 domain

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

Similar variants

APBA2 p.Ile614= Likely benign same residue
APBA2 p.Val77Met Uncertain significance ★★ ⚠ same type
APBA2 c.1216-9T>C Benign ★★ same type
APBA2 c.1525-8C>G Likely benign ★★ same type
APBA2 c.1705-9C>T Benign ★★ same type
APBA2 p.Asp87= Benign ★★ same type
APBA2 p.Gly206= Benign ★★ same type
APBA2 p.His127= Benign ★★ 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/apba2-p-ile614val (accessed [today's date]).

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