Is WIPF1 p.Pro283= (c.849C>T) pathogenic?

WIPF1 p.Pro283= (c.849C>T) is classified Likely benign in WIPF1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-12-19). Very rare (popmax 0.000258%, nfe); Associated with Wiskott-Aldrich syndrome 2.

What condition is associated with WIPF1 p.Pro283= (c.849C>T)?

WIPF1 p.Pro283= (c.849C>T) is associated with Wiskott-Aldrich syndrome 2 (ClinVar).

How common is WIPF1 p.Pro283= (c.849C>T) in the general population?

WIPF1 p.Pro283= (c.849C>T) is very rare (popmax 0.000258%, nfe) (gnomAD).

WIPF1 p.Pro283=

c.849C>T · VCV3674072

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.000258%, 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 -7.7	GERP -2.6
Overall
CADD	0.049	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000258% European (non-Finnish) · 3/1,161,614 alleles

Filtering AF 6.9e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.9e-05%

Overall 0.000191% 3/1,574,632 alleles · very rare exomes 3/1,422,412 · genomes 0/152,220 · joint denominator

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.Pro283=
Coding: c.849C>T
MANE Select: NM_001375834
Type: single nucleotide variant
Location: chr2:174571956 (GRCh38)
Gene constraint: LOEUF 0.565 · pLI 0.83 (gnomAD)
Structure: AlphaFold pLDDT 59.19 · 5 PDB
Residue 283: 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.Pro283Arg Uncertain significance ★★ ⚠ same residue
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

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-pro283 (accessed [today's date]).

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