Is WDR26 p.Pro511Ser (c.1531C>T) pathogenic?

WDR26 p.Pro511Ser (c.1531C>T) is classified Uncertain significance in WDR26 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-03-10). AlphaMissense: ambiguous (0.3921); Absent from gnomAD v4.1.

How common is WDR26 p.Pro511Ser (c.1531C>T) in the general population?

WDR26 p.Pro511Ser (c.1531C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about WDR26 p.Pro511Ser (c.1531C>T)?

AlphaMissense predicts ambiguous (score 0.3921) — an in-silico prediction, not a clinical call.

WDR26 p.Pro511Ser

c.1531C>T · VCV4881600

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3921 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

REVEL, SaProt · AlphaMissense indeterminate

Computational evidence

Protein change
AlphaMissense	0.3921	ambiguous
REVEL	0.689	pathogenic-leaning
SaProt	LLR -10.54	damaging
⇒ REVEL and SaProt both call this damaging; AlphaMissense is indeterminate.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 12	GERP 2.3, phastCons 1
Regional constraint	o/e 0.52	unconstrained · MANE · 44 kb · p 2.4e-35 · regional, not allelic
Overall
CADD	32.0	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM P411S vs ClinVar P511S) — verify the residue.

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: WDR26
Protein: p.Pro511Ser
Coding: c.1531C>T
MANE Select: NM_001379403
Type: single nucleotide variant
Location: chr1:224404498 (GRCh38)
Gene constraint: LOEUF 0.144 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 81.30 · 4 PDB
Residue 411 UniProt numbering: a UniProt-annotated variant site (in skdeas); a UniProt-annotated variant site (in skdeas; uncertain significance)

Full WDR26 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

WDR26 p.Pro511Ala Uncertain significance ★ ⚠ same residue
WDR26 p.Asp735Gly Pathogenic/Likely pathogenic ★★ same type
WDR26 p.Ala137Val Uncertain significance ★★ ⚠ same type
WDR26 p.Ala154Pro Uncertain significance ★★ ⚠ same type
WDR26 p.Arg639Gln Uncertain significance ★★ same type
WDR26 p.Glu526Asp Uncertain significance ★★ ⚠ same type
WDR26 p.Ile481Met Uncertain significance ★★ same type
WDR26 p.Leu490Val Uncertain significance ★★ ⚠ same type

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/wdr26-p-pro511ser (accessed [today's date]).

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