Is WRN p.Phe810fs (c.2427dup) pathogenic?

WRN p.Phe810fs (c.2427dup) is classified Pathogenic in WRN (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-14). Ultra-rare (gnomAD MAF 1.427e-06); Associated with Werner syndrome.

What condition is associated with WRN p.Phe810fs (c.2427dup)?

WRN p.Phe810fs (c.2427dup) is associated with Werner syndrome (ClinVar).

How common is WRN p.Phe810fs (c.2427dup) in the general population?

WRN p.Phe810fs (c.2427dup) is ultra-rare (gnomAD MAF 1.427e-06) (gnomAD).

How is Werner syndrome inherited?

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

WRN p.Phe810fs

c.2427dup · rs2130306151 · VCV2767130

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

ultra-rare (gnomAD MAF 1.427e-06)

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 20 of 35
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 5.2	GERP 1.6, phastCons 0.98

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

Population frequency

dbSNP / gnomAD

Global frequency 0.000143% via dbSNP · ultra-rare

No ancestry breakdown or filtering allele frequency is available for this variant, so BA1/BS1 cannot be assessed from this figure alone.

Variant & gene context

Gene: WRN
Protein: p.Phe810fs
Coding: c.2427dup
MANE Select: NM_000553
dbSNP: rs2130306151
Type: Duplication
Location: chr8:31116505 (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 810: an α-helix; the helicase c-terminal domain

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.Phe810Leu 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
WRN p.Thr1044fs Pathogenic ★★ same condition
WRN p.Tyr110Ter 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/wrn-p-phe810fs (accessed [today's date]).

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