Is ANKRD26 p.Pro490Ser (c.1468C>T) pathogenic?

ANKRD26 p.Pro490Ser (c.1468C>T) is classified Uncertain significance in ANKRD26 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-02-15). AlphaMissense: likely benign (0.0938); Very rare (popmax 0.000537%, nfe); Associated with Inborn genetic diseases.

What condition is associated with ANKRD26 p.Pro490Ser (c.1468C>T)?

ANKRD26 p.Pro490Ser (c.1468C>T) is associated with Inborn genetic diseases (ClinVar).

How common is ANKRD26 p.Pro490Ser (c.1468C>T) in the general population?

ANKRD26 p.Pro490Ser (c.1468C>T) is very rare (popmax 0.000537%, nfe) (gnomAD).

What do computational predictors say about ANKRD26 p.Pro490Ser (c.1468C>T)?

AlphaMissense predicts likely benign (score 0.0938) — an in-silico prediction, not a clinical call.

ANKRD26 p.Pro490Ser

c.1468C>T · rs767456225 · VCV2173669

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.0938 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000537%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0938	likely benign
REVEL	0.058	moderately benign-leaning
SaProt	LLR -5.41	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -0.18
Regional constraint	o/e 1.00	unconstrained · MANE · 65 kb · p 0.96 · regional, not allelic
Overall
CADD	13.12	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

Grpmax group 0.000537% European (non-Finnish) · 6/1,117,808 alleles

Filtering AF 0.000193% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000127%

Overall 0.000389% 6/1,540,744 alleles · very rare exomes 5/1,388,650 · genomes 1/152,094 · joint denominator

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.Pro490Ser
Coding: c.1468C>T
MANE Select: NM_014915
dbSNP: rs767456225
Type: single nucleotide variant
Location: chr10:27060535 (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.Pro490Leu Uncertain significance ★ ⚠ same residue
ANKRD26 p.Pro490Thr Uncertain significance ★ ⚠ same residue
ANKRD26 p.Pro490= Likely benign ★ 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

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-pro490ser (accessed [today's date]).

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