Is ANKRD23 p.Ala172Val (c.515C>T) pathogenic?

ANKRD23 p.Ala172Val (c.515C>T) is classified Uncertain significance in ANKRD23 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-06-11). AlphaMissense: likely benign (0.2109); Rare (popmax 0.109%, eas).

How common is ANKRD23 p.Ala172Val (c.515C>T) in the general population?

ANKRD23 p.Ala172Val (c.515C>T) is rare (popmax 0.109%, eas) (gnomAD).

What do computational predictors say about ANKRD23 p.Ala172Val (c.515C>T)?

AlphaMissense predicts likely benign (score 0.2109) — an in-silico prediction, not a clinical call.

ANKRD23 p.Ala172Val

c.515C>T · VCV3296710

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2109 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.109%, eas)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2109	likely benign
REVEL	0.091	moderately benign-leaning
SaProt	LLR -10.16	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.9	GERP -0.38, phastCons 0.22
Regional constraint	o/e 1.04	unconstrained · MANE · 4,440 bp · p 0.43 · regional, not allelic
Overall
CADD	14.55	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 0.109% East Asian · 49/44,900 alleles

Filtering AF 0.0848% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0761%

Overall 0.00421% 68/1,613,886 alleles · rare exomes 66/1,461,666 · genomes 2/152,220 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.109%	916
Middle Eastern	0.0165%	6,072
Remaining individualsnot grpmax-eligible	0.0032%	31,243
South Asian	0.0022%	45,532
European (non-Finnish)	0.00119%	84,287

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: ANKRD23
Protein: p.Ala172Val
Coding: c.515C>T
MANE Select: NM_144994
Type: single nucleotide variant
Location: chr2:96840426 (GRCh38)
Gene constraint: LOEUF 1.671 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.08

Full ANKRD23 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ANKRD23 p.Ala172Thr Uncertain significance ★ ⚠ same residue
ANKRD23 p.Ala166Ser Uncertain significance ★ ⚠ same type
ANKRD23 p.Ala238Thr Uncertain significance ★ ⚠ same type
ANKRD23 p.Ala43Val Uncertain significance ★ ⚠ same type
ANKRD23 p.Ala73Gly Uncertain significance ★ ⚠ same type
ANKRD23 p.Ala73Pro Uncertain significance ★ ⚠ same type
ANKRD23 p.Arg145Cys Uncertain significance ★ ⚠ same type
ANKRD23 p.Arg206Gln 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/ankrd23-p-ala172val (accessed [today's date]).

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