Is WASF2 p.Pro334Ser (c.1000C>T) pathogenic?

WASF2 p.Pro334Ser (c.1000C>T) is classified Likely benign in WASF2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-21). AlphaMissense: likely benign (0.0973); Very rare (popmax 0.00989%, sas).

How common is WASF2 p.Pro334Ser (c.1000C>T) in the general population?

WASF2 p.Pro334Ser (c.1000C>T) is very rare (popmax 0.00989%, sas) (gnomAD).

What do computational predictors say about WASF2 p.Pro334Ser (c.1000C>T)?

AlphaMissense predicts likely benign (score 0.0973) — an in-silico prediction, not a clinical call.

WASF2 p.Pro334Ser

c.1000C>T · VCV4200095

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0973 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00989%, sas)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0973	likely benign
REVEL	0.089	moderately benign-leaning
SaProt	LLR -10.10	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.6	GERP -0.92, phastCons 1
Regional constraint	o/e 0.77	unconstrained · MANE · 6,664 bp · p 6e-06 · regional, not allelic
Overall
CADD	15.0	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

Grpmax group 0.00989% South Asian · 9/91,018 alleles

Filtering AF 0.00514% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00376%

Overall 0.000868% 14/1,613,686 alleles · very rare exomes 13/1,461,606 · genomes 1/152,080 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00989%	10,113
Remaining individualsnot grpmax-eligible	0.0032%	31,237
East Asian	0.00223%	44,888
European (non-Finnish)	0.00017%	589,943

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: WASF2
Protein: p.Pro334Ser
Coding: c.1000C>T
MANE Select: NM_006990
Type: single nucleotide variant
Location: chr1:27410031 (GRCh38)
Gene constraint: LOEUF 0.464 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 68.74 · 1 PDB
Residue 334: the 'disordered' region

Full WASF2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

WASF2 p.Pro247Leu Likely benign ★★ same type
WASF2 p.Ala317Val Uncertain significance ★ ⚠ same type
WASF2 p.Ala372Ser Uncertain significance ★ ⚠ same type
WASF2 p.Arg451Cys Uncertain significance ★ ⚠ same type
WASF2 p.Arg64Trp Uncertain significance ★ ⚠ same type
WASF2 p.Arg74Gln Uncertain significance ★ ⚠ same type
WASF2 p.Asn135Ser Uncertain significance ★ ⚠ same type
WASF2 p.Asn59Asp Uncertain significance ★ ⚠ 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/wasf2-p-pro334ser (accessed [today's date]).

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