Is WDR81 p.Val993Ala (c.2978T>C) pathogenic?

WDR81 p.Val993Ala (c.2978T>C) is classified Uncertain significance in WDR81 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-12-11). AlphaMissense: likely benign (0.1791); Very rare (popmax 0.00588%, amr); Associated with Inborn genetic diseases.

What condition is associated with WDR81 p.Val993Ala (c.2978T>C)?

WDR81 p.Val993Ala (c.2978T>C) is associated with Inborn genetic diseases (ClinVar).

How common is WDR81 p.Val993Ala (c.2978T>C) in the general population?

WDR81 p.Val993Ala (c.2978T>C) is very rare (popmax 0.00588%, amr) (gnomAD).

What do computational predictors say about WDR81 p.Val993Ala (c.2978T>C)?

AlphaMissense predicts likely benign (score 0.1791) — an in-silico prediction, not a clinical call.

WDR81 p.Val993Ala

c.2978T>C · VCV3816169

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1791 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00588%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1791	likely benign
REVEL	0.244	benign-leaning
SaProt	LLR -2.67	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6.2	GERP 1.4, phastCons 1
Regional constraint	o/e 0.94	unconstrained · MANE · 11 kb · p 0.014 · regional, not allelic
Overall
CADD	22.8	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00588% Admixed American · 3/50,990 alleles

Filtering AF 0.00386% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00347%

Overall 0.004% 62/1,550,288 alleles · very rare exomes 53/1,398,078 · genomes 9/152,210 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00588%	16,997
European (non-Finnish)	0.00488%	20,482
Remaining individualsnot grpmax-eligible	0.00333%	30,050
African / African-American	0.00137%	73,060

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.Val993Ala
Coding: c.2978T>C
MANE Select: NM_001163809
Type: single nucleotide variant
Location: chr17:1727937 (GRCh38)
Gene constraint: LOEUF 0.817 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 69.23

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-val993ala (accessed [today's date]).

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