Is WFS1 p.Pro279= (c.837T>G) pathogenic?

WFS1 p.Pro279= (c.837T>G) is classified Benign in WFS1 (ClinVar, Single submitter, 1 submitter). Absent from gnomAD v4.1; Associated with Wolfram syndrome 1.

What condition is associated with WFS1 p.Pro279= (c.837T>G)?

WFS1 p.Pro279= (c.837T>G) is associated with Wolfram syndrome 1 (ClinVar).

How common is WFS1 p.Pro279= (c.837T>G) in the general population?

WFS1 p.Pro279= (c.837T>G) is absent from gnomAD v4.1 (gnomAD).

How is Wolfram syndrome inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

WFS1 p.Pro279=

c.837T>G · rs762770133 · VCV1810362

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

Wolfram syndrome 1

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.034	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -15	GERP -2.4
Overall
CADD	1.798	PHRED · no single calibrated threshold — expert panels disagree

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: WFS1
Protein: p.Pro279=
Coding: c.837T>G
MANE Select: NM_006005
dbSNP: rs762770133
Type: single nucleotide variant
Location: chr4:6295165 (GRCh38)
Gene constraint: LOEUF 1.64 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 73.85
Residue 279: the 'interaction with atp6v1a' region

Full WFS1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Wolfram syndrome 1 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Wolfram syndrome (Orphanet):

Inheritance: Autosomal recessive
Onset: Adolescent, Adult, Childhood
Prevalence: 1-9 / 1 000 000 (United Kingdom)

Similar variants

WFS1 p.Pro279Arg Uncertain significance ★ ⚠ same residue
WFS1 p.Pro279Leu Uncertain significance ★ ⚠ same residue
WFS1 c.233-1G>C Pathogenic/Likely pathogenic ★★ same condition
WFS1 c.460+1G>A Pathogenic ★★ same condition
WFS1 c.861+2T>C Pathogenic ★★ same condition
WFS1 p.Ala126Thr Pathogenic/Likely pathogenic ★★ same condition
WFS1 p.Ala684Val Pathogenic/Likely pathogenic ★★ ⚠ same condition
WFS1 p.Ala716Thr Pathogenic/Likely pathogenic ★★ ⚠ 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/wfs1-p-pro279 (accessed [today's date]).

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