Is ANKRD26 p.Met1237Thr (c.3710T>C) pathogenic?

ANKRD26 p.Met1237Thr (c.3710T>C) is classified Conflicting classifications of pathogenicity in ANKRD26 (ClinVar, Conflicting submitters, 5 submitters; last evaluated 2026-01-24). AlphaMissense: likely pathogenic (0.9699); Ultra-rare (popmax 0.0912%, sas); Associated with thrombocytopenia 2.

What condition is associated with ANKRD26 p.Met1237Thr (c.3710T>C)?

ANKRD26 p.Met1237Thr (c.3710T>C) is associated with thrombocytopenia 2 (ClinVar).

How common is ANKRD26 p.Met1237Thr (c.3710T>C) in the general population?

ANKRD26 p.Met1237Thr (c.3710T>C) is ultra-rare (popmax 0.0912%, sas) (gnomAD).

What do computational predictors say about ANKRD26 p.Met1237Thr (c.3710T>C)?

AlphaMissense predicts likely pathogenic (score 0.9699) — an in-silico prediction, not a clinical call.

ANKRD26 p.Met1237Thr

c.3710T>C · rs760695730 · VCV1337895

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 5 submitters

AlphaMissense

likely pathogenic

0.9699 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0912%, sas)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

thrombocytopenia 2

Computational evidence

Protein change
AlphaMissense	0.9699	likely pathogenic · top 1% in ANKRD26
REVEL	0.331	indeterminate
SaProt	LLR -5.65	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.23	GERP -2.4
Regional constraint	o/e 0.95	unconstrained · MANE · 30 kb · p 0.17 · regional, not allelic
Overall
CADD	22.7	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 0.0912% South Asian · 83/90,970 alleles

Filtering AF 0.0753% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0695%

Overall 0.00533% 86/1,612,414 alleles · ultra-rare exomes 84/1,460,294 · genomes 2/152,120 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0912%	1,096
Middle Eastern	0.0165%	6,076
Remaining individualsnot grpmax-eligible	0.00321%	31,197

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: ANKRD26
Protein: p.Met1237Thr
Coding: c.3710T>C
MANE Select: NM_014915
dbSNP: rs760695730
Type: single nucleotide variant
Location: chr10:27033322 (GRCh38)
Gene constraint: LOEUF 0.728 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 62.91

Full ANKRD26 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

thrombocytopenia 2 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

ANKRD26 p.Met1237Lys Uncertain significance ★ ⚠ same residue
ANKRD26 p.Met1237Val Uncertain significance ★ ⚠ same residue
ANKRD26 c.-118C>T Pathogenic/Likely pathogenic ★★ same condition
ANKRD26 c.-126T>C Pathogenic/Likely pathogenic ★★ same condition
ANKRD26 c.-127A>T Pathogenic/Likely pathogenic ★★ same condition
ANKRD26 c.-128G>A Pathogenic/Likely pathogenic ★★ same condition
ANKRD26 c.-128G>T Pathogenic/Likely pathogenic ★★ same condition
ANKRD26 c.-134G>A Pathogenic/Likely pathogenic ★★ 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/ankrd26-p-met1237thr (accessed [today's date]).

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