Is WASF1 p.Ser91Pro (c.271T>C) pathogenic?

WASF1 p.Ser91Pro (c.271T>C) is classified Uncertain significance in WASF1 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-08-08). AlphaMissense: likely pathogenic (0.9805); Very rare (popmax 0.00017%, nfe); Associated with Inborn genetic diseases.

What condition is associated with WASF1 p.Ser91Pro (c.271T>C)?

WASF1 p.Ser91Pro (c.271T>C) is associated with Inborn genetic diseases (ClinVar).

How common is WASF1 p.Ser91Pro (c.271T>C) in the general population?

WASF1 p.Ser91Pro (c.271T>C) is very rare (popmax 0.00017%, nfe) (gnomAD).

What do computational predictors say about WASF1 p.Ser91Pro (c.271T>C)?

AlphaMissense predicts likely pathogenic (score 0.9805) — an in-silico prediction, not a clinical call.

WASF1 p.Ser91Pro

c.271T>C · rs2534230026 · VCV2305834

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9805 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00017%, nfe)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.9805	likely pathogenic
REVEL	0.444	indeterminate
SaProt	LLR -10.87	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL is indeterminate.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 11	GERP 3.6, phastCons 1
Regional constraint	o/e 0.54	unconstrained · MANE · 22 kb · p 8.4e-14 · regional, not allelic
Overall
CADD	25.6	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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 0.00017% European (non-Finnish) · 2/1,178,296 alleles

Filtering AF 2.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000124% 2/1,609,276 alleles · very rare exomes 2/1,456,916 · genomes 0/152,360 · 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: WASF1
Protein: p.Ser91Pro
Coding: c.271T>C
MANE Select: NM_003931
dbSNP: rs2534230026
Type: single nucleotide variant
Location: chr6:110108679 (GRCh38)
Gene constraint: LOEUF 0.301 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 67.26 · 5 PDB

Full WASF1 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

WASF1 p.Met165Leu Uncertain significance ★★ ⚠ same condition
WASF1 p.Pro350Ala Uncertain significance ★★ ⚠ same condition
WASF1 p.Pro350Ser Uncertain significance ★★ ⚠ same condition
WASF1 p.Asn57Ser Likely benign ★★ same condition
WASF1 p.Thr105Ala Likely benign ★★ same condition
WASF1 p.Thr446Pro Likely benign ★★ same condition
WASF1 c.893+3A>T Uncertain significance ★ same condition
WASF1 p.Ala385Ser 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/wasf1-p-ser91pro (accessed [today's date]).

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