Is WDR26 p.Pro486= (c.1458G>A) pathogenic?

WDR26 p.Pro486= (c.1458G>A) is classified Uncertain significance in WDR26 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-03-10). Very rare (popmax 0.00017%, nfe); Associated with Skraban-Deardorff syndrome.

What condition is associated with WDR26 p.Pro486= (c.1458G>A)?

WDR26 p.Pro486= (c.1458G>A) is associated with Skraban-Deardorff syndrome (ClinVar).

How common is WDR26 p.Pro486= (c.1458G>A) in the general population?

WDR26 p.Pro486= (c.1458G>A) is very rare (popmax 0.00017%, nfe) (gnomAD).

WDR26 p.Pro486=

Q: How is Intellectual disability-seizures-abnormal gait-facial dysmorphism syndrome inherited?

Typically Autosomal dominant (Orphanet). A genetic counselor can assess individual risk for a family.

c.1458G>A · rs144934464 · VCV3236041

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00017%, nfe)

Conditions

Skraban-Deardorff syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
REVEL	0.061	moderately benign-leaning
Splicing
SpliceAI	Δ0.31	donor gain · deltas
Constraint at this position
Conservation	phyloP 3.3	GERP 2.5, phastCons 1
Overall
CADD	24.5	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00017% European (non-Finnish) · 2/1,177,758 alleles

Filtering AF 2.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000124% 2/1,607,386 alleles · very rare exomes 2/1,455,224 · genomes 0/152,162 · 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: WDR26
Protein: p.Pro486=
Coding: c.1458G>A
MANE Select: NM_001379403
dbSNP: rs144934464
Type: single nucleotide variant
Location: chr1:224411427 (GRCh38)
Gene constraint: LOEUF 0.144 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 81.30 · 4 PDB
Residue 486: 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

Disease context

Skraban-Deardorff syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Intellectual disability-seizures-abnormal gait-facial dysmorphism syndrome (Orphanet):

Inheritance: Autosomal dominant
Onset: Infancy

Similar variants

WDR26 p.Pro486Leu Uncertain significance ★★ ⚠ same residue
WDR26 p.Pro486Thr Uncertain significance ★ ⚠ same residue
WDR26 p.Asp735Gly Pathogenic/Likely pathogenic ★★ same condition
WDR26 p.Ala154Pro Uncertain significance ★★ ⚠ same condition
WDR26 p.Arg639Gln Uncertain significance ★★ same condition
WDR26 p.Leu490Val Uncertain significance ★★ ⚠ same condition
WDR26 p.Ser165Phe Uncertain significance ★★ ⚠ same condition
WDR26 p.Thr452Met 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/wdr26-p-pro486 (accessed [today's date]).

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