GLS p.Val495=
c.1485T>C · VCV4959162
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0164%, mid)
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 0.84 | GERP 0.28, phastCons 1 |
| Overall | ||
| CADD | 9.397 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0164%
Middle Eastern · 1/6,080 alleles
Filtering AF
0.00662%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00483%
Overall
0.00155%
25/1,611,378 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.0164% | 6,080 |
| Admixed American | 0.0133% | 7,493 |
| Remaining individualsnot grpmax-eligible | 0.00801% | 12,483 |
| European (non-Finnish) | 0.000934% | 107,069 |
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
- GLS
- Protein
- p.Val495=
- Coding
- c.1485T>C
- MANE Select
- NM_013267 · reported on NM_014905
- Type
- single nucleotide variant
- Location
- chr2:190930496 (GRCh38)
- Structure
- AlphaFold pLDDT 85.66 · 4 PDB
- Residue 495
- an α-helix
Similar variants
- GLS2 p.Tyr495Cys Uncertain significance ★ ⚠ same residue
- GLS p.Ala99Thr Uncertain significance ★★ ⚠ same type
- GLS p.Leu25Arg Uncertain significance ★★ ⚠ same type
- GLS c.387-3T>C Likely benign ★★ same type
- GLS p.Ala561= Benign ★★ same type
- GLS p.Arg53= Likely benign ★★ same type
- GLS p.Pro313= Likely benign ★★ same type
- GLS p.Val554= Likely benign ★★ same type
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/gls-p-val495 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown