Is WIPF1 p.Pro256= (c.768C>T) pathogenic?

WIPF1 p.Pro256= (c.768C>T) is classified Likely benign in WIPF1 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-11-09). Very rare (popmax 0.00443%, nfe); Associated with Wiskott-Aldrich syndrome 2.

What condition is associated with WIPF1 p.Pro256= (c.768C>T)?

WIPF1 p.Pro256= (c.768C>T) is associated with Wiskott-Aldrich syndrome 2 (ClinVar).

How common is WIPF1 p.Pro256= (c.768C>T) in the general population?

WIPF1 p.Pro256= (c.768C>T) is very rare (popmax 0.00443%, nfe) (gnomAD).

WIPF1 p.Pro256=

c.768C>T · rs775538363 · VCV1102370

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00443%, nfe)

Conditions

Wiskott-Aldrich syndrome 2

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -5.9	GERP -2.6
Overall
CADD	0.857	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00443% European (non-Finnish) · 51/1,150,178 alleles

Filtering AF 0.00343% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0031%

Overall 0.00362% 56/1,548,336 alleles · very rare

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	0.00492%	20,337
European (non-Finnish)grpmax	0.00443%	22,552
Remaining individualsnot grpmax-eligible	0.00336%	29,798

Finnish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Pro256=
Coding: c.768C>T
MANE Select: NM_001375834
dbSNP: rs775538363
Type: single nucleotide variant
Location: chr2:174572037 (GRCh38)
Gene constraint: LOEUF 0.565 · pLI 0.83 (gnomAD)
Structure: AlphaFold pLDDT 59.19 · 5 PDB
Residue 256: 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-pro256 (accessed [today's date]).

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