Is WASF2 p.Pro391Ser (c.1171C>T) pathogenic?

WASF2 p.Pro391Ser (c.1171C>T) is classified Uncertain significance in WASF2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-10). AlphaMissense: likely benign (0.1205); Ultra-rare (popmax 0.0123%, nfe).

How common is WASF2 p.Pro391Ser (c.1171C>T) in the general population?

WASF2 p.Pro391Ser (c.1171C>T) is ultra-rare (popmax 0.0123%, nfe) (gnomAD).

What do computational predictors say about WASF2 p.Pro391Ser (c.1171C>T)?

AlphaMissense predicts likely benign (score 0.1205) — an in-silico prediction, not a clinical call.

WASF2 p.Pro391Ser

c.1171C>T · VCV4200101

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1205 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0123%, nfe)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.1205	likely benign
REVEL	0.371	indeterminate
SaProt	LLR -10.88	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6.9	GERP 0.21, phastCons 1
Regional constraint	o/e 0.77	unconstrained · MANE · 6,664 bp · p 6e-06 · regional, not allelic
Overall
CADD	21.0	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 0.0123% European (non-Finnish) · 141/1,145,878 alleles

Filtering AF 0.0106% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.01%

Overall 0.0158% 245/1,553,504 alleles · ultra-rare

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	0.138%	727
Remaining individualsnot grpmax-eligible	0.0317%	3,154
European (non-Finnish)grpmax	0.0123%	8,127

Finnish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Pro391Ser
Coding: c.1171C>T
MANE Select: NM_006990
Type: single nucleotide variant
Location: chr1:27409860 (GRCh38)
Gene constraint: LOEUF 0.464 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 68.74 · 1 PDB
Residue 391: 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-pro391ser (accessed [today's date]).

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