Is ANKRD26 p.Gln20Arg (c.59A>G) pathogenic?

ANKRD26 p.Gln20Arg (c.59A>G) is classified Benign/Likely benign in ANKRD26 (ClinVar, Multiple submitters, 11 submitters; last evaluated 2026-02-04). AlphaMissense: likely benign (0.0604); Common (popmax 100%, eas) — too common for a highly-penetrant pathogenic allele; Associated with thrombocytopenia 2.

What condition is associated with ANKRD26 p.Gln20Arg (c.59A>G)?

ANKRD26 p.Gln20Arg (c.59A>G) is associated with thrombocytopenia 2 (ClinVar).

What do computational predictors say about ANKRD26 p.Gln20Arg (c.59A>G)?

AlphaMissense predicts likely benign (score 0.0604) — an in-silico prediction, not a clinical call.

ANKRD26 p.Gln20Arg

Q: How common is ANKRD26 p.Gln20Arg (c.59A>G) in the general population?

ANKRD26 p.Gln20Arg (c.59A>G) is common (popmax 100%, eas) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.59A>G · rs7897309 · VCV260472

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 11 submitters

AlphaMissense

likely benign

0.0604 · ACMG-weighted

gnomAD v4.1

Common

common (popmax 100%, eas) — too common for a highly-penetrant pathogenic allele

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

thrombocytopenia 2

Computational evidence

Protein change
AlphaMissense	0.0604	likely benign
REVEL	0.005	strongly benign-leaning
SaProt	LLR -4.66	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 -5.5	GERP -2.6
Regional constraint	o/e 1.00	unconstrained · MANE · 65 kb · p 0.96 · regional, not allelic
Overall
CADD	0.076	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 100% East Asian · 44,836/44,850 alleles

Filtering AF 99.2% ClinGen BA1/BS1 input FAF95, joint · FAF99 98.9%

Overall 87.1% 1,402,334/1,610,676 alleles · common

Ancestry group	Frequency	1 in
East Asiangrpmax	100%	1
African / African-American	97.4%	1
Finnishnot grpmax-eligible	92.6%	1
Admixed American	92.2%	1
South Asian	91.8%	1
Remaining individualsnot grpmax-eligible	87.9%	1
Ashkenazi Jewishnot grpmax-eligible	87.5%	1
Middle Eastern	86.5%	1
European (non-Finnish)	85%	1
Amishnot grpmax-eligible	82.9%	1

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.Gln20Arg
Coding: c.59A>G
MANE Select: NM_014915
dbSNP: rs7897309
Type: single nucleotide variant
Location: chr10:27100268 (GRCh38)
Gene constraint: LOEUF 0.728 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 62.91
Residue 20: a UniProt-annotated variant site (in); the 'disordered' region

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.Gln20= 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-gln20arg (accessed [today's date]).

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