Is ANKRD26 p.Met1237Val (c.3709A>G) pathogenic?

ANKRD26 p.Met1237Val (c.3709A>G) is classified Uncertain significance in ANKRD26 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-11-22). AlphaMissense: ambiguous (0.4725); Ultra-rare (popmax 0.0357%, eas); Associated with Inborn genetic diseases.

What condition is associated with ANKRD26 p.Met1237Val (c.3709A>G)?

ANKRD26 p.Met1237Val (c.3709A>G) is associated with Inborn genetic diseases (ClinVar).

How common is ANKRD26 p.Met1237Val (c.3709A>G) in the general population?

ANKRD26 p.Met1237Val (c.3709A>G) is ultra-rare (popmax 0.0357%, eas) (gnomAD).

What do computational predictors say about ANKRD26 p.Met1237Val (c.3709A>G)?

AlphaMissense predicts ambiguous (score 0.4725) — an in-silico prediction, not a clinical call.

ANKRD26 p.Met1237Val

c.3709A>G · VCV3396105

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4725 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0357%, eas)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense indeterminate

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.4725	ambiguous
REVEL	0.287	benign-leaning
SaProt	LLR -5.50	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.18	GERP 1.8
Regional constraint	o/e 0.95	unconstrained · MANE · 30 kb · p 0.17 · regional, not allelic
Overall
CADD	21.8	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 0.0357% East Asian · 16/44,772 alleles

Filtering AF 0.0224% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0182%

Overall 0.00105% 17/1,612,394 alleles · ultra-rare exomes 16/1,460,240 · genomes 1/152,154 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0357%	2,798
South Asian	0.0011%	90,970

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.Met1237Val
Coding: c.3709A>G
MANE Select: NM_014915
Type: single nucleotide variant
Location: chr10:27033323 (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.Met1237Lys 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-met1237val (accessed [today's date]).

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