Is WRN p.Pro87fs (c.254_258dup) pathogenic?

WRN p.Pro87fs (c.254258dup) is classified Likely pathogenic in WRN (ClinVar, Single submitter, 1 submitter; last evaluated 2023-09-27). No gnomAD frequency available for this variant; Associated with Werner syndrome.

What condition is associated with WRN p.Pro87fs (c.254_258dup)?

WRN p.Pro87fs (c.254_258dup) is associated with Werner syndrome (ClinVar).

How common is WRN p.Pro87fs (c.254_258dup) in the general population?

WRN p.Pro87fs (c.254_258dup) is no gnomAD frequency available for this variant (gnomAD).

How is Werner syndrome inherited?

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

WRN p.Pro87fs

c.254_258dup · rs2535880796 · VCV2679587

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

Werner syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 4 of 35
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 7.8	GERP 1.8, phastCons 1

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: WRN
Protein: p.Pro87fs
Coding: c.254_258dup
MANE Select: NM_000553
dbSNP: rs2535880796
Type: Duplication
Location: chr8:31064332 (GRCh38)
Gene constraint: LOEUF 0.9 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 68.75 · 51 PDB
Residue 87: the 3'-5' exonuclease domain; the 'interaction with wrnip1' region

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

Disease context

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

For Werner syndrome (Orphanet):

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

Similar variants

WRN p.Pro87= Likely benign ★★ same residue
WRN p.Pro87Ala Uncertain significance ★ ⚠ same residue
WRN p.Pro87Leu Uncertain significance ★ ⚠ same residue
WRN c.1576+1dup Likely pathogenic ★★ same condition
WRN p.Ala1137fs Pathogenic/Likely pathogenic ★★ same condition
WRN p.Glu411fs Pathogenic/Likely pathogenic ★★ same condition
WRN p.Ile665fs Pathogenic/Likely pathogenic ★★ same condition
WRN p.Ile673fs 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/wrn-p-pro87fs (accessed [today's date]).

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