WRN p.Asp441=
c.1323T>C · rs2535916929 · VCV2009101
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Absent
absent from gnomAD v4.1
Conditions
1
Werner syndrome
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 2.7 | GERP 1.3, phastCons 1 |
| Overall | ||
| CADD | 7.686 | 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
- WRN
- Protein
- p.Asp441=
- Coding
- c.1323T>C
- MANE Select
- NM_000553
- dbSNP
- rs2535916929
- Type
- single nucleotide variant
- Location
- chr8:31083752 (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 441
- an α-helix; the '2 x 27 aa tandem repeats of h-l-s-p-n-d-n-e-n-d-t-s-y-v-i-e-s-d-e-d-l-e-m-e-m-l-k' region
Disease context
Werner syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatmentsFor Werner syndrome (Orphanet):
- Inheritance
- Autosomal recessive
- Onset
- Adolescent, Adult
- Prevalence
- 1-9 / 1 000 000 (Europe)
Similar variants
- WRN p.Asp441fs Pathogenic ★ same residue
- WRN p.Asp441del Uncertain significance ★ same residue
- WRN c.1351-1G>A Likely pathogenic ★★ same condition
- WRN c.1351-2A>G Likely pathogenic ★★ same condition
- WRN c.1432-2A>T Likely pathogenic ★★ same condition
- WRN c.1652+1G>A Likely pathogenic ★★ same condition
- WRN c.1720+5G>A Likely pathogenic ★★ same condition
- WRN c.1721-1G>A 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-asp441 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown