Is WASF2 p.Pro400Ser (c.1198C>T) pathogenic?

WASF2 p.Pro400Ser (c.1198C>T) is classified Uncertain significance in WASF2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-10-11). AlphaMissense: likely benign (0.2023); Very rare (popmax 0.0029%, sas).

How common is WASF2 p.Pro400Ser (c.1198C>T) in the general population?

WASF2 p.Pro400Ser (c.1198C>T) is very rare (popmax 0.0029%, sas) (gnomAD).

What do computational predictors say about WASF2 p.Pro400Ser (c.1198C>T)?

AlphaMissense predicts likely benign (score 0.2023) — an in-silico prediction, not a clinical call.

WASF2 p.Pro400Ser

c.1198C>T · VCV3468966

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2023 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0029%, sas)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2023	likely benign
REVEL	0.169	moderately benign-leaning
SaProt	LLR -11.33	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>T here scores Δ0.29 · evaluated, not missing
Constraint at this position
Conservation	phyloP 8.2	GERP -2.2, phastCons 1
Regional constraint	o/e 0.77	unconstrained · MANE · 6,664 bp · p 6e-06 · regional, not allelic
Overall
CADD	21.2	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 0.0029% South Asian · 2/68,946 alleles

Filtering AF 0.000481% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00018%

Overall 0.000135% 2/1,485,752 alleles · very rare exomes 2/1,333,844 · genomes 0/151,908 · joint denominator

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.Pro400Ser
Coding: c.1198C>T
MANE Select: NM_006990
Type: single nucleotide variant
Location: chr1:27409833 (GRCh38)
Gene constraint: LOEUF 0.464 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 68.74 · 1 PDB
Residue 400: the 'disordered' region

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

Similar variants

WASF2 p.Pro400Leu Uncertain significance ★ ⚠ same residue
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

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-pro400ser (accessed [today's date]).

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