Is ANKRD2 p.Ala10Val (c.29C>T) pathogenic?

ANKRD2 p.Ala10Val (c.29C>T) is classified Uncertain significance in ANKRD2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-15). AlphaMissense: likely benign (0.1272); Ultra-rare (popmax 0.0188%, eas).

How common is ANKRD2 p.Ala10Val (c.29C>T) in the general population?

ANKRD2 p.Ala10Val (c.29C>T) is ultra-rare (popmax 0.0188%, eas) (gnomAD).

What do computational predictors say about ANKRD2 p.Ala10Val (c.29C>T)?

AlphaMissense predicts likely benign (score 0.1272) — an in-silico prediction, not a clinical call.

ANKRD2 p.Ala10Val

c.29C>T · rs147018759 · VCV3123897

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1272 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0188%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1272	likely benign
REVEL	0.008	strongly benign-leaning
SaProt	LLR -6.63	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 2	GERP 2.1, phastCons 0.94
Regional constraint	o/e 0.92	unconstrained · MANE · 11 kb · p 0.092 · regional, not allelic
Overall
CADD	14.89	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.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM A37V vs ClinVar A10V) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0188% East Asian · 8/42,546 alleles

Filtering AF 0.0104% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00821%

Overall 0.0042% 66/1,570,578 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0188%	5,318
African / African-American	0.0175%	5,700
Admixed American	0.00755%	13,253
South Asian	0.00703%	14,232
Remaining individualsnot grpmax-eligible	0.00493%	20,266
European (non-Finnish)	0.00276%	36,197

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: ANKRD2
Protein: p.Ala10Val
Coding: c.29C>T
MANE Select: NM_001346793
dbSNP: rs147018759
Type: single nucleotide variant
Location: chr10:97572817 (GRCh38)
Gene constraint: LOEUF 1.426 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.30
Residue 10: the 'may mediate interaction with pml, p53/tp53 and ybx1' region

Full ANKRD2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ANKRD2 p.Ala285= Benign ★★ same type
ANKRD2 p.Pro119Leu Benign/Likely benign ★★ ⚠ same type
ANKRD2 p.Pro6Arg Benign ★★ same type
ANKRD2 p.Ala128Val Uncertain significance ★ ⚠ same type
ANKRD2 p.Ala12Thr Uncertain significance ★ ⚠ same type
ANKRD2 p.Ala311Val Uncertain significance ★ ⚠ same type
ANKRD2 p.Arg100Pro Uncertain significance ★ ⚠ same type
ANKRD2 p.Arg155Gln 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/ankrd2-p-ala10val (accessed [today's date]).

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