Is WFS1 p.Phe384= (c.1152C>T) pathogenic?

WFS1 p.Phe384= (c.1152C>T) is classified Conflicting classifications of pathogenicity in WFS1 (ClinVar, Conflicting submitters, 10 submitters; last evaluated 2026-01-05). Rare (popmax 0.245%, eas); Associated with autosomal dominant nonsyndromic hearing loss 6.

What condition is associated with WFS1 p.Phe384= (c.1152C>T)?

WFS1 p.Phe384= (c.1152C>T) is associated with autosomal dominant nonsyndromic hearing loss 6, Wolfram syndrome 1 (ClinVar).

How common is WFS1 p.Phe384= (c.1152C>T) in the general population?

WFS1 p.Phe384= (c.1152C>T) is rare (popmax 0.245%, eas) (gnomAD).

WFS1 p.Phe384=

c.1152C>T · rs149846741 · VCV178589

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 10 submitters

gnomAD v4.1

Rare

rare (popmax 0.245%, eas)

Conditions

autosomal dominant nonsyndromic hearing loss 6

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 -3.4	GERP -0.64
Overall
CADD	8.716	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.245% East Asian · 110/44,870 alleles

Filtering AF 0.208% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.194%

Overall 0.021% 339/1,614,046 alleles · rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.245%	408
African / African-American	0.092%	1,087
Middle Eastern	0.033%	3,031
Remaining individualsnot grpmax-eligible	0.0176%	5,683
Admixed American	0.0167%	5,990
European (non-Finnish)	0.0109%	9,147
South Asian	0.00769%	13,011
Finnishnot grpmax-eligible	0.00156%	64,042

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.Phe384=
Coding: c.1152C>T
MANE Select: NM_006005
dbSNP: rs149846741
Type: single nucleotide variant
Location: chr4:6300947 (GRCh38)
Gene constraint: LOEUF 1.64 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 73.85

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

Disease context

autosomal dominant nonsyndromic hearing loss 6 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: Wolfram syndrome 1

Similar variants

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
WFS1 p.Arg26Ter Pathogenic/Likely pathogenic ★★ same condition
WFS1 p.Arg42Ter 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-phe384 (accessed [today's date]).

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