Is ANKRD26 p.Pro274Arg (c.821C>G) pathogenic?

ANKRD26 p.Pro274Arg (c.821C>G) is classified Uncertain significance in ANKRD26 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-02-24). AlphaMissense: likely benign (0.1642); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with ANKRD26 p.Pro274Arg (c.821C>G)?

ANKRD26 p.Pro274Arg (c.821C>G) is associated with Inborn genetic diseases, thrombocytopenia 2 (ClinVar).

How common is ANKRD26 p.Pro274Arg (c.821C>G) in the general population?

ANKRD26 p.Pro274Arg (c.821C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ANKRD26 p.Pro274Arg (c.821C>G)?

AlphaMissense predicts likely benign (score 0.1642) — an in-silico prediction, not a clinical call.

ANKRD26 p.Pro274Arg

c.821C>G · rs1589347239 · VCV1710955

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1642 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1642	likely benign
REVEL	0.09	moderately benign-leaning
SaProt	LLR -6.12	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 1.3	GERP -0.32
Regional constraint	o/e 1.00	unconstrained · MANE · 65 kb · p 0.96 · regional, not allelic
Overall
CADD	14.67	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.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: ANKRD26
Protein: p.Pro274Arg
Coding: c.821C>G
MANE Select: NM_014915
dbSNP: rs1589347239
Type: single nucleotide variant
Location: chr10:27077686 (GRCh38)
Gene constraint: LOEUF 0.728 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 62.91
Residue 274: the 'disordered' region

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

Also linked: thrombocytopenia 2

Similar variants

ANKRD26 p.Pro274= Likely benign ★ 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
ANKRD26 c.4724+2T>A 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-pro274arg (accessed [today's date]).

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