GLS p.Pro493=
c.1479C>G · VCV3390338
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0361%, afr)
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 -0.15 | GERP -1.1, phastCons 0.34 |
| Overall | ||
| CADD | 8.449 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0361%
African / African-American · 27/74,892 alleles
Filtering AF
0.0254%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0219%
Overall
0.00298%
48/1,610,652 alleles · ultra-rare
exomes 39/1,458,478 · genomes 9/152,174 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.0361% | 2,774 |
| Remaining individualsnot grpmax-eligible | 0.0336% | 2,973 |
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.Pro493=
- Coding
- c.1479C>G
- MANE Select
- NM_014905
- Type
- single nucleotide variant
- Location
- chr2:190930490 (GRCh38)
- Structure
- AlphaFold pLDDT 85.66 · 4 PDB
- Residue 493
- an α-helix
Similar variants
- 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
- GLS2 p.Gly337= 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-pro493 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown