Is WFS1 p.Ser32= (c.96G>A) pathogenic?

WFS1 p.Ser32= (c.96G>A) is classified Benign/Likely benign in WFS1 (ClinVar, Multiple submitters, 10 submitters; last evaluated 2026-01-08). Rare (popmax 0.339%, afr); Associated with Wolfram syndrome 1.

What condition is associated with WFS1 p.Ser32= (c.96G>A)?

WFS1 p.Ser32= (c.96G>A) is associated with Wolfram syndrome 1, WFS1-related disorder (ClinVar).

How common is WFS1 p.Ser32= (c.96G>A) in the general population?

WFS1 p.Ser32= (c.96G>A) is rare (popmax 0.339%, afr) (gnomAD).

How is Wolfram syndrome inherited?

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

WFS1 p.Ser32=

c.96G>A · rs71539660 · VCV166566

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 10 submitters

gnomAD v4.1

Rare

rare (popmax 0.339%, afr)

Conditions

Wolfram syndrome 1

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 -12	GERP -2.8
Overall
CADD	0.065	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.339% African / African-American · 253/74,728 alleles

Filtering AF 0.304% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.291%

Overall 0.0185% 294/1,590,242 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.339%	295
Middle Eastern	0.0498%	2,010
Admixed American	0.0229%	4,361
Remaining individualsnot grpmax-eligible	0.0178%	5,605
East Asian	0.00456%	21,953
South Asian	0.00115%	87,128
European (non-Finnish)	0.000941%	106,280

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: WFS1
Protein: p.Ser32=
Coding: c.96G>A
MANE Select: NM_006005
dbSNP: rs71539660
Type: single nucleotide variant
Location: chr4:6277551 (GRCh38)
Gene constraint: LOEUF 1.64 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 73.85
Residue 32: the 'interaction with atp6v1a' region; the 'disordered' region; a modified residue (phosphoserine; by fam20c)

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

Also linked: WFS1-related disorder

For Wolfram syndrome (Orphanet):

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

Similar variants

WFS1 p.Ser32Ter Likely pathogenic ★ same residue
WFS1 c.233-1G>C Pathogenic/Likely pathogenic ★★ same condition
WFS1 c.460+1G>A Pathogenic ★★ same condition
WFS1 c.861+1G>A Pathogenic/Likely 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-ser32 (accessed [today's date]).

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