Is WDFY3 p.Arg697Cys (c.2089C>T) pathogenic?

WDFY3 p.Arg697Cys (c.2089C>T) is classified Uncertain significance in WDFY3 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-29). AlphaMissense: likely pathogenic (0.9036); Very rare (popmax 0.00668%, eas); Associated with Inborn genetic diseases.

What condition is associated with WDFY3 p.Arg697Cys (c.2089C>T)?

WDFY3 p.Arg697Cys (c.2089C>T) is associated with Inborn genetic diseases (ClinVar).

How common is WDFY3 p.Arg697Cys (c.2089C>T) in the general population?

WDFY3 p.Arg697Cys (c.2089C>T) is very rare (popmax 0.00668%, eas) (gnomAD).

What do computational predictors say about WDFY3 p.Arg697Cys (c.2089C>T)?

AlphaMissense predicts likely pathogenic (score 0.9036) — an in-silico prediction, not a clinical call.

WDFY3 p.Arg697Cys

c.2089C>T · VCV4200300

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9036 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00668%, eas)

Conditions

Inborn genetic diseases

⚠ Built without this gene's context — gene constraint and dosage, protein structure, pathways, panels and related-variant links were not looked up for this page. why

Computational evidence

Protein change
AlphaMissense	0.9036	likely pathogenic
REVEL	0.541	indeterminate
SaProt	—	not scored · why
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 12	GERP 2.5, phastCons 1
Regional constraint	o/e 0.78	unconstrained · MANE · 80 kb · p 7.3e-20 · regional, not allelic
Overall
CADD	31.0	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL is an independent agreement signal.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00668% East Asian · 3/44,896 alleles

Filtering AF 0.00255% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00161%

Overall 0.0013% 21/1,614,006 alleles · very rare exomes 18/1,461,852 · genomes 3/152,154 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00668%	14,965
African / African-American	0.00667%	14,983
Remaining individualsnot grpmax-eligible	0.0016%	62,484
European (non-Finnish)	0.00102%	98,333

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: WDFY3
Protein: p.Arg697Cys
Coding: c.2089C>T
MANE Select: NM_014991
Type: single nucleotide variant
Location: chr4:84810143 (GRCh38)

Full WDFY3 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

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/wdfy3-p-arg697cys (accessed [today's date]).

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