Is ANKRD26 p.Met1237Lys (c.3710T>A) pathogenic?

ANKRD26 p.Met1237Lys (c.3710T>A) is classified Uncertain significance in ANKRD26 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-07-09). AlphaMissense: likely pathogenic (0.9505); Very rare (popmax 0.00267%, afr); Associated with Inborn genetic diseases.

What condition is associated with ANKRD26 p.Met1237Lys (c.3710T>A)?

ANKRD26 p.Met1237Lys (c.3710T>A) is associated with Inborn genetic diseases (ClinVar).

How common is ANKRD26 p.Met1237Lys (c.3710T>A) in the general population?

ANKRD26 p.Met1237Lys (c.3710T>A) is very rare (popmax 0.00267%, afr) (gnomAD).

What do computational predictors say about ANKRD26 p.Met1237Lys (c.3710T>A)?

AlphaMissense predicts likely pathogenic (score 0.9505) — an in-silico prediction, not a clinical call.

ANKRD26 p.Met1237Lys

c.3710T>A · VCV4103369

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9505 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00267%, afr)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.9505	likely pathogenic · top 1% in ANKRD26
REVEL	0.426	indeterminate
SaProt	LLR -5.19	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call.
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	23.1	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 0.00267% African / African-American · 2/74,892 alleles

Filtering AF 0.000443% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000166%

Overall 0.000124% 2/1,612,414 alleles · very rare exomes 1/1,460,294 · genomes 1/152,120 · joint denominator

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.Met1237Lys
Coding: c.3710T>A
MANE Select: NM_014915
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

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

ANKRD26 p.Met1237Val Uncertain significance ★ ⚠ same residue
ANKRD26 p.Met1237Thr Conflicting classifications of pathogenicity ★ ⚠ same residue
ANKRD26 p.Ala1014Ser Uncertain significance ★★ ⚠ same condition
ANKRD26 p.Ala1015Val Uncertain significance ★★ ⚠ same condition
ANKRD26 p.Ala120Thr Uncertain significance ★★ ⚠ same condition
ANKRD26 p.Ala1215Thr Uncertain significance ★★ ⚠ same condition
ANKRD26 p.Ala1284Ser Uncertain significance ★★ ⚠ same condition
ANKRD26 p.Ala1416Val Uncertain significance ★★ ⚠ 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-met1237lys (accessed [today's date]).

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