DES p.Phe119Ser
c.356T>C · VCV4959974
Likely pathogenic
Single submitter
Classification
Likely pathogenic
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
AlphaMissense
likely pathogenic
0.9997 · ACMG-weighted
gnomAD v4.1
Absent
absent from gnomAD v4.1
Missense predictors
3/3 damaging
AlphaMissense, REVEL, SaProt
Conditions
1
DES-related disorders
Computational evidence
| Protein change | ||
| AlphaMissense | 0.9997 | likely pathogenic ✓ concordant with ClinVar · top 1% in DES |
|---|---|---|
| REVEL | 0.965 | strongly pathogenic-leaning |
| SaProt | LLR -14.69 | damaging |
| ⇒ AlphaMissense, REVEL and SaProt all call this damaging. | ||
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 7.7 | GERP 1.9, phastCons 1 |
| Regional constraint | o/e 0.92 | unconstrained · MANE · 7,524 bp · p 0.05 · regional, not allelic |
| Overall | ||
| CADD | 34.0 | PHRED · no single calibrated threshold — expert panels disagree |
AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.
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
- DES
- Protein
- p.Phe119Ser
- Coding
- c.356T>C
- MANE Select
- NM_001927
- Type
- single nucleotide variant
- Location
- chr2:219418818 (GRCh38)
- Gene constraint
- LOEUF 0.81 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 77.73
- Residue 119
- the if rod domain; the 'coil 1a' region
Disease context
DES-related disorders
Similar variants
- DES p.Phe119= Likely benign ★★ same residue
- DES p.Phe119Tyr Uncertain significance ★ ⚠ same residue
- DES c.736-1G>A Likely pathogenic ★★ same condition
- DES p.Arg406Trp Pathogenic/Likely pathogenic ★★ same condition
- DES p.Asn116Ser Pathogenic/Likely pathogenic ★★ same condition
- DES p.Glu401Lys Likely pathogenic ★★ same condition
- DES p.Glu413Lys Pathogenic/Likely pathogenic ★★ same condition
- DES p.Leu345Pro 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/des-p-phe119ser (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown