GLS p.Ala45=
c.135C>A · VCV4959142
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
low-frequency (popmax 3.73%, sas)
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 -0.33 | GERP -2 |
| Overall | ||
| CADD | 7.29 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
3.73%
South Asian · 1,089/29,230 alleles
Filtering AF
3.54%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 3.47%
Overall
0.0943%
1,175/1,246,470 alleles · low-frequency
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 3.73% | 27 |
| Middle Eastern | 0.187% | 535 |
| Remaining individualsnot grpmax-eligible | 0.138% | 726 |
| African / African-American | 0.00782% | 12,789 |
| Admixed American | 0.00429% | 23,300 |
| East Asian | 0.00326% | 30,720 |
| European (non-Finnish) | 0.001% | 99,859 |
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.Ala45=
- Coding
- c.135C>A
- MANE Select
- NM_013267 · reported on NM_014905
- Type
- single nucleotide variant
- Location
- chr2:190881219 (GRCh38)
- Structure
- AlphaFold pLDDT 85.66 · 4 PDB
- Residue 45
- the 'disordered' region
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-ala45 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown