Is WDR81 p.Pro600= (c.1800C>T) pathogenic?

WDR81 p.Pro600= (c.1800C>T) is classified Likely benign in WDR81 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-08-27). Ultra-rare (popmax 0.0123%, afr); Associated with WDR81-related disorder.

What condition is associated with WDR81 p.Pro600= (c.1800C>T)?

WDR81 p.Pro600= (c.1800C>T) is associated with WDR81-related disorder (ClinVar).

How common is WDR81 p.Pro600= (c.1800C>T) in the general population?

WDR81 p.Pro600= (c.1800C>T) is ultra-rare (popmax 0.0123%, afr) (gnomAD).

WDR81 p.Pro600=

c.1800C>T · rs772179388 · VCV3053492

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0123%, afr)

Conditions

WDR81-related disorder

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 -6	GERP -4.7
Overall
CADD	0.31	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0123% African / African-American · 9/73,022 alleles

Filtering AF 0.00638% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00478%

Overall 0.00181% 28/1,547,534 alleles · ultra-rare exomes 21/1,395,348 · genomes 7/152,186 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0123%	8,114
East Asian	0.00978%	10,226
Remaining individualsnot grpmax-eligible	0.00167%	60,012
European (non-Finnish)	0.00122%	81,888

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.Pro600=
Coding: c.1800C>T
MANE Select: NM_001163809
dbSNP: rs772179388
Type: single nucleotide variant
Location: chr17:1726759 (GRCh38)
Gene constraint: LOEUF 0.817 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 69.23
Residue 600: 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

Disease context

WDR81-related disorder

Similar variants

WDR81 p.Pro600Leu Uncertain significance ★ ⚠ same residue
WDR81 p.Arg397Ter Likely pathogenic ★★ same condition
WDR81 p.Gly1681Ser Uncertain significance ★★ ⚠ same condition
WDR81 p.Gln145Ter Likely pathogenic ★ same condition
WDR81 p.Lys1603Ter Likely pathogenic ★ same condition
WDR81 p.Glu536Lys Uncertain significance ⚠ same condition
WDR81 p.Lys1134Gln Uncertain significance ⚠ same condition
WDR81 p.Ala685= Likely benign 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/wdr81-p-pro600 (accessed [today's date]).

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