GLS p.Arg53=
c.159A>G · VCV3388912
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
very rare (popmax 0.00508%, nfe)
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 -0.004 | GERP -1, phastCons 0.53 |
| Overall | ||
| CADD | 14.84 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00508%
European (non-Finnish) · 51/1,003,178 alleles
Filtering AF
0.00393%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00355%
Overall
0.0043%
54/1,254,982 alleles · very rare
exomes 48/1,104,536 · genomes 6/150,446 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.00508% | 19,670 |
| Remaining individualsnot grpmax-eligible | 0.00432% | 23,134 |
| Finnishnot grpmax-eligible | 0.00284% | 35,228 |
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.Arg53=
- Coding
- c.159A>G
- MANE Select
- NM_014905
- Type
- single nucleotide variant
- Location
- chr2:190881243 (GRCh38)
- Structure
- AlphaFold pLDDT 85.66 · 4 PDB
- Residue 53
- the 'disordered' region
Similar variants
- GLS2 p.Ser53Cys 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.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-arg53 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown