Is ANKRD30A p.Val89Ile (c.265G>A) pathogenic?

ANKRD30A p.Val89Ile (c.265G>A) is classified Uncertain significance in ANKRD30A (ClinVar, Single submitter, 1 submitter; last evaluated 2023-05-18). AlphaMissense: likely benign (0.2655); Ultra-rare (popmax 0.0164%, eas).

How common is ANKRD30A p.Val89Ile (c.265G>A) in the general population?

ANKRD30A p.Val89Ile (c.265G>A) is ultra-rare (popmax 0.0164%, eas) (gnomAD).

What do computational predictors say about ANKRD30A p.Val89Ile (c.265G>A)?

AlphaMissense predicts likely benign (score 0.2655) — an in-silico prediction, not a clinical call.

ANKRD30A p.Val89Ile

c.265G>A · rs534812137 · VCV2548837

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2655 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0164%, eas)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.2655	likely benign
REVEL	0.333	indeterminate
SaProt	LLR -8.69	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.2	GERP 1.8, phastCons 1
Regional constraint	o/e 1.10	unconstrained · MANE · 39 kb · p 0.0028 · regional, not allelic
Overall
CADD	19.89	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 0.0164% East Asian · 7/42,808 alleles

Filtering AF 0.00767% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00534%

Overall 0.000762% 12/1,574,878 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0164%	6,115
Remaining individualsnot grpmax-eligible	0.00826%	12,103

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: ANKRD30A
Protein: p.Val89Ile
Coding: c.265G>A
MANE Select: NM_052997
dbSNP: rs534812137
Type: single nucleotide variant
Location: chr10:37129936 (GRCh38)
Gene constraint: LOEUF 1.295 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 56.16 · 1 PDB

Full ANKRD30A gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ANKRD30A p.Ala1006Val Uncertain significance ★ ⚠ same type
ANKRD30A p.Ala1119Gly Uncertain significance ★ ⚠ same type
ANKRD30A p.Ala120Val Uncertain significance ★ ⚠ same type
ANKRD30A p.Ala1226Glu Uncertain significance ★ ⚠ same type
ANKRD30A p.Ala122Val Uncertain significance ★ ⚠ same type
ANKRD30A p.Ala1273Gly Uncertain significance ★ ⚠ same type
ANKRD30A p.Ala1298Ser Uncertain significance ★ ⚠ same type
ANKRD30A p.Ala146Thr 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/ankrd30a-p-val89ile (accessed [today's date]).

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