Is WDR81 p.Ser577Arg (c.1731C>G) pathogenic?

WDR81 p.Ser577Arg (c.1731C>G) is classified Uncertain significance in WDR81 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-05-29). AlphaMissense: likely pathogenic (0.8937); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with WDR81 p.Ser577Arg (c.1731C>G)?

WDR81 p.Ser577Arg (c.1731C>G) is associated with Inborn genetic diseases (ClinVar).

How common is WDR81 p.Ser577Arg (c.1731C>G) in the general population?

WDR81 p.Ser577Arg (c.1731C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about WDR81 p.Ser577Arg (c.1731C>G)?

AlphaMissense predicts likely pathogenic (score 0.8937) — an in-silico prediction, not a clinical call.

WDR81 p.Ser577Arg

c.1731C>G · VCV3332968

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8937 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.8937	likely pathogenic
REVEL	0.562	indeterminate
SaProt	LLR -2.18	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.8	GERP 2.4, phastCons 1
Regional constraint	o/e 0.94	unconstrained · MANE · 11 kb · p 0.014 · regional, not allelic
Overall
CADD	22.0	PHRED · no single calibrated threshold — expert panels disagree

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

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: WDR81
Protein: p.Ser577Arg
Coding: c.1731C>G
MANE Select: NM_001163809
Type: single nucleotide variant
Location: chr17:1726690 (GRCh38)
Gene constraint: LOEUF 0.817 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 69.23
Residue 577: 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

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

WDR81 p.Arg1779Ter Pathogenic ★★ same condition
WDR81 p.Ala1015Thr Uncertain significance ★★ ⚠ same condition
WDR81 p.Ala1029Thr Uncertain significance ★★ ⚠ same condition
WDR81 p.Ala1514Val Uncertain significance ★★ same condition
WDR81 p.Ala1515Val Uncertain significance ★★ ⚠ same condition
WDR81 p.Ala273Thr Uncertain significance ★★ ⚠ same condition
WDR81 p.Ala280Val Uncertain significance ★★ ⚠ same condition
WDR81 p.Ala429Ser 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/wdr81-p-ser577arg (accessed [today's date]).

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