Is WASF2 p.Asp486Val (c.1457A>T) pathogenic?

WASF2 p.Asp486Val (c.1457A>T) is classified Uncertain significance in WASF2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-04-23). AlphaMissense: likely pathogenic (0.9352); Absent from gnomAD v4.1.

How common is WASF2 p.Asp486Val (c.1457A>T) in the general population?

WASF2 p.Asp486Val (c.1457A>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about WASF2 p.Asp486Val (c.1457A>T)?

AlphaMissense predicts likely pathogenic (score 0.9352) — an in-silico prediction, not a clinical call.

WASF2 p.Asp486Val

c.1457A>T · VCV3332559

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9352 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.9352	likely pathogenic
REVEL	0.534	indeterminate
SaProt	LLR -11.18	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL is indeterminate.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · T>C here scores Δ0.82 · evaluated, not missing
Constraint at this position
Conservation	phyloP 7.9	GERP 2.4, phastCons 1
Regional constraint	o/e 0.77	unconstrained · MANE · 6,664 bp · p 6e-06 · regional, not allelic
Overall
CADD	26.6	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: WASF2
Protein: p.Asp486Val
Coding: c.1457A>T
MANE Select: NM_006990
Type: single nucleotide variant
Location: chr1:27408229 (GRCh38)
Gene constraint: LOEUF 0.464 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 68.74 · 1 PDB

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-asp486val (accessed [today's date]).

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