Is WASF1 p.Pro442Ser (c.1324C>T) pathogenic?

WASF1 p.Pro442Ser (c.1324C>T) is classified Uncertain significance in WASF1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-07-31). AlphaMissense: likely benign (0.0794); Ultra-rare (popmax 0.0165%, mid); Associated with Inborn genetic diseases.

What condition is associated with WASF1 p.Pro442Ser (c.1324C>T)?

WASF1 p.Pro442Ser (c.1324C>T) is associated with Inborn genetic diseases (ClinVar).

How common is WASF1 p.Pro442Ser (c.1324C>T) in the general population?

WASF1 p.Pro442Ser (c.1324C>T) is ultra-rare (popmax 0.0165%, mid) (gnomAD).

What do computational predictors say about WASF1 p.Pro442Ser (c.1324C>T)?

AlphaMissense predicts likely benign (score 0.0794) — an in-silico prediction, not a clinical call.

WASF1 p.Pro442Ser

c.1324C>T · VCV4200086

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0794 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0165%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0794	likely benign
REVEL	0.239	benign-leaning
SaProt	LLR -7.09	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 8.7	GERP 2.7, phastCons 1
Regional constraint	o/e 0.86	unconstrained · MANE · 3,828 bp · p 0.0076 · regional, not allelic
Overall
CADD	20.3	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — 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 0.0165% Middle Eastern · 1/6,062 alleles

Filtering AF 0.000615% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000474%

Overall 0.00118% 19/1,614,152 alleles · ultra-rare exomes 19/1,461,864 · genomes 0/152,288 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0165%	6,062
Ashkenazi Jewishnot grpmax-eligible	0.0135%	7,401
Remaining individualsnot grpmax-eligible	0.0016%	62,504
European (non-Finnish)	0.0011%	90,771

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.Pro442Ser
Coding: c.1324C>T
MANE Select: NM_003931
Type: single nucleotide variant
Location: chr6:110101786 (GRCh38)
Gene constraint: LOEUF 0.301 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 67.26 · 5 PDB
Residue 442: the 'disordered' region

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-pro442ser (accessed [today's date]).

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