Is ANKRD26 p.Pro1627Ser (c.4879C>T) pathogenic?

ANKRD26 p.Pro1627Ser (c.4879C>T) is classified Conflicting classifications of pathogenicity in ANKRD26 (ClinVar, Conflicting submitters, 7 submitters; last evaluated 2026-02-11). AlphaMissense: likely benign (0.177); Ultra-rare (popmax 0.0617%, amr); Associated with thrombocytopenia 2.

What condition is associated with ANKRD26 p.Pro1627Ser (c.4879C>T)?

ANKRD26 p.Pro1627Ser (c.4879C>T) is associated with thrombocytopenia 2 (ClinVar).

How common is ANKRD26 p.Pro1627Ser (c.4879C>T) in the general population?

ANKRD26 p.Pro1627Ser (c.4879C>T) is ultra-rare (popmax 0.0617%, amr) (gnomAD).

What do computational predictors say about ANKRD26 p.Pro1627Ser (c.4879C>T)?

AlphaMissense predicts likely benign (score 0.177) — an in-silico prediction, not a clinical call.

ANKRD26 p.Pro1627Ser

c.4879C>T · rs572143624 · VCV299726

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 7 submitters

AlphaMissense

likely benign

0.177 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0617%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

thrombocytopenia 2

Computational evidence

Protein change
AlphaMissense	0.177	likely benign
REVEL	0.277	benign-leaning
SaProt	LLR -4.95	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	GERP 0.015
Regional constraint	o/e 0.95	unconstrained · MANE · 30 kb · p 0.17 · regional, not allelic
Overall
CADD	19.21	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 0.0617% Admixed American · 37/60,014 alleles

Filtering AF 0.0459% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0405%

Overall 0.00328% 53/1,614,074 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0617%	1,622
Middle Eastern	0.0165%	6,062
Ashkenazi Jewishnot grpmax-eligible	0.0135%	7,401
Remaining individualsnot grpmax-eligible	0.0032%	31,252
African / African-American	0.00267%	37,509
European (non-Finnish)	0.000593%	168,568

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.Pro1627Ser
Coding: c.4879C>T
MANE Select: NM_014915
dbSNP: rs572143624
Type: single nucleotide variant
Location: chr10:27012956 (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 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
ANKRD26 c.4725-10A>G 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-pro1627ser (accessed [today's date]).

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