Is WIPF1 p.Ser460= (c.1380C>T) pathogenic?

WIPF1 p.Ser460= (c.1380C>T) is classified Conflicting classifications of pathogenicity in WIPF1 (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2025-10-21). Ultra-rare (popmax 0.0841%, afr); Associated with Wiskott-Aldrich syndrome 2.

What condition is associated with WIPF1 p.Ser460= (c.1380C>T)?

WIPF1 p.Ser460= (c.1380C>T) is associated with Wiskott-Aldrich syndrome 2 (ClinVar).

How common is WIPF1 p.Ser460= (c.1380C>T) in the general population?

WIPF1 p.Ser460= (c.1380C>T) is ultra-rare (popmax 0.0841%, afr) (gnomAD).

WIPF1 p.Ser460=

c.1380C>T · rs753915750 · VCV540145

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0841%, afr)

Conditions

Wiskott-Aldrich syndrome 2

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>T here scores Δ0.24 · evaluated, not missing
Constraint at this position
Conservation	phyloP 0.73	GERP -3.1, phastCons 0.95
Overall
CADD	11.7	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0841% African / African-American · 63/74,932 alleles

Filtering AF 0.0674% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0614%

Overall 0.00551% 89/1,614,108 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0841%	1,189
Middle Eastern	0.0164%	6,084
Remaining individualsnot grpmax-eligible	0.0064%	15,621
Admixed American	0.00333%	30,007
South Asian	0.00329%	30,364
European (non-Finnish)	0.00136%	73,753

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: WIPF1
Protein: p.Ser460=
Coding: c.1380C>T
MANE Select: NM_001375834
dbSNP: rs753915750
Type: single nucleotide variant
Location: chr2:174567146 (GRCh38)
Gene constraint: LOEUF 0.565 · pLI 0.83 (gnomAD)
Structure: AlphaFold pLDDT 59.19 · 5 PDB
Residue 460: the 'disordered' region

Full WIPF1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Wiskott-Aldrich syndrome 2 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

WIPF1 p.Ala259Val Uncertain significance ★★ ⚠ same condition
WIPF1 p.Ala281Pro Uncertain significance ★★ ⚠ same condition
WIPF1 p.Arg125Gln Uncertain significance ★★ ⚠ same condition
WIPF1 p.Arg201Trp Uncertain significance ★★ ⚠ same condition
WIPF1 p.Arg393Trp Uncertain significance ★★ ⚠ same condition
WIPF1 p.Arg485Gln Uncertain significance ★★ ⚠ same condition
WIPF1 p.Arg485Trp Uncertain significance ★★ ⚠ same condition
WIPF1 p.Asn19His 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/wipf1-p-ser460 (accessed [today's date]).

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