Is WDR81 p.Pro488= (c.1464G>A) pathogenic?

WDR81 p.Pro488= (c.1464G>A) is classified Likely benign in WDR81 (ClinVar, Single submitter, 1 submitter; last evaluated 2026-04-01). Very rare (popmax 0.00788%, amr).

How common is WDR81 p.Pro488= (c.1464G>A) in the general population?

WDR81 p.Pro488= (c.1464G>A) is very rare (popmax 0.00788%, amr) (gnomAD).

WDR81 p.Pro488=

c.1464G>A · VCV4872949

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00788%, amr)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -11	GERP -4.9
Overall
CADD	0.197	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00788% Admixed American · 4/50,770 alleles

Filtering AF 0.00264% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00154%

Overall 0.00394% 61/1,547,764 alleles · very rare exomes 57/1,397,806 · genomes 4/149,958 · joint denominator

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	0.0909%	1,100
Remaining individualsnot grpmax-eligible	0.0167%	6,004
Admixed Americangrpmax	0.00788%	12,692
South Asian	0.00238%	41,933
European (non-Finnish)	0.00166%	60,322

Ashkenazi Jewish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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: WDR81
Protein: p.Pro488=
Coding: c.1464G>A
MANE Select: NM_001163809
Type: single nucleotide variant
Location: chr17:1726423 (GRCh38)
Gene constraint: LOEUF 0.817 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 69.23
Residue 488: the beach domain; the 'necessary and sufficient for the interaction with sqstm1' region

Full WDR81 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

WDR81 p.Pro488Leu Uncertain significance ★ ⚠ same residue
WDR81 p.Arg1333Ter Pathogenic/Likely pathogenic ★★ same type
WDR81 p.Arg1779Ter Pathogenic ★★ same type
WDR81 p.Arg397Ter Likely pathogenic ★★ same type
WDR81 p.Gln1096Ter Pathogenic ★★ same type
WDR81 p.Pro856Leu Pathogenic/Likely pathogenic ★★ ⚠ same type
WDR81 p.Tyr1257Ter Pathogenic/Likely pathogenic ★★ same type
WDR81 p.Tyr1281Ter Pathogenic/Likely pathogenic ★★ 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/wdr81-p-pro488 (accessed [today's date]).

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