Is ANKRD26 p.Pro259Ser (c.775C>T) pathogenic?

ANKRD26 p.Pro259Ser (c.775C>T) is classified Uncertain significance in ANKRD26 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-12-29). AlphaMissense: ambiguous (0.3726); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with ANKRD26 p.Pro259Ser (c.775C>T)?

ANKRD26 p.Pro259Ser (c.775C>T) is associated with Inborn genetic diseases (ClinVar).

How common is ANKRD26 p.Pro259Ser (c.775C>T) in the general population?

ANKRD26 p.Pro259Ser (c.775C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ANKRD26 p.Pro259Ser (c.775C>T)?

AlphaMissense predicts ambiguous (score 0.3726) — an in-silico prediction, not a clinical call.

ANKRD26 p.Pro259Ser

c.775C>T · VCV4842355

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3726 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.3726	ambiguous
REVEL	0.075	moderately benign-leaning
SaProt	LLR -3.22	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.06	GERP 0.007
Regional constraint	o/e 1.00	unconstrained · MANE · 65 kb · p 0.96 · regional, not allelic
Overall
CADD	21.7	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

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.Pro259Ser
Coding: c.775C>T
MANE Select: NM_014915
Type: single nucleotide variant
Location: chr10:27079127 (GRCh38)
Gene constraint: LOEUF 0.728 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 62.91
Residue 259: 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

Similar variants

ANKRD26 p.Pro259Leu Uncertain significance ★ ⚠ same residue
ANKRD26 p.Pro259Thr Uncertain significance ★ ⚠ same residue
ANKRD26 p.Pro259= Likely benign ★ same residue
ANKRD26 p.Pro259Ala Uncertain significance ★ ⚠ 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

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-pro259ser (accessed [today's date]).

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