Is WASF1 p.Pro349Ser (c.1045C>T) pathogenic?

WASF1 p.Pro349Ser (c.1045C>T) is classified Likely benign in WASF1 (ClinVar, Single submitter, 2 submitters; last evaluated 2024-08-20). AlphaMissense: likely benign (0.1571); Rare (popmax 0.53%, afr).

How common is WASF1 p.Pro349Ser (c.1045C>T) in the general population?

WASF1 p.Pro349Ser (c.1045C>T) is rare (popmax 0.53%, afr) (gnomAD).

What do computational predictors say about WASF1 p.Pro349Ser (c.1045C>T)?

AlphaMissense predicts likely benign (score 0.1571) — an in-silico prediction, not a clinical call.

WASF1 p.Pro349Ser

c.1045C>T · rs147654100 · VCV3051343

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1571 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.53%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1571	likely benign
REVEL	0.239	benign-leaning
SaProt	LLR -8.95	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 12	GERP 3.4, phastCons 1
Regional constraint	o/e 0.86	unconstrained · MANE · 3,828 bp · p 0.0076 · regional, not allelic
Overall
CADD	22.4	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 0.53% African / African-American · 379/71,556 alleles

Filtering AF 0.486% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.468%

Overall 0.0264% 400/1,516,136 alleles · rare exomes 173/1,364,414 · genomes 227/151,722 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.53%	189
Remaining individualsnot grpmax-eligible	0.0189%	5,295
Admixed American	0.0181%	5,523
South Asian	0.00134%	74,842
European (non-Finnish)	8.82e-05%	1,133,374

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.Pro349Ser
Coding: c.1045C>T
MANE Select: NM_003931
dbSNP: rs147654100
Type: single nucleotide variant
Location: chr6:110102065 (GRCh38)
Gene constraint: LOEUF 0.301 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 67.26 · 5 PDB
Residue 349: the 'disordered' region

Full WASF1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

WASF1 p.Arg506Ter Pathogenic ★★ same type
WASF1 p.Arg102Ter Uncertain significance ★★ same type
WASF1 p.Arg538His Uncertain significance ★★ ⚠ same type
WASF1 p.Met165Leu Uncertain significance ★★ ⚠ same type
WASF1 p.Pro280Leu Uncertain significance ★★ ⚠ same type
WASF1 p.Pro350Ala Uncertain significance ★★ ⚠ same type
WASF1 p.Pro350Ser Uncertain significance ★★ ⚠ same type
WASF1 p.Asn57Ser Likely benign ★★ 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/wasf1-p-pro349ser (accessed [today's date]).

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