Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Common
common (popmax 5.16%, eas) — too common for a highly-penetrant pathogenic allele
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 -10 | GERP -3.7 |
| Overall | ||
| CADD | 0.127 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
5.16%
East Asian · 2,312/44,848 alleles
Filtering AF
4.98%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 4.91%
Overall
0.315%
5,071/1,611,020 alleles · common
exomes 4,195/1,458,714 · genomes 876/152,306 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 5.16% | 19 |
| Admixed American | 2.64% | 38 |
| South Asian | 0.725% | 138 |
| Remaining individualsnot grpmax-eligible | 0.486% | 206 |
| African / African-American | 0.12% | 833 |
| Ashkenazi Jewishnot grpmax-eligible | 0.0372% | 2,689 |
| Middle Eastern | 0.0165% | 6,052 |
| European (non-Finnish) | 0.009% | 11,106 |
| Finnishnot grpmax-eligible | 0.00312% | 32,006 |
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.Ala561=
- Coding
- c.1683A>C
- MANE Select
- NM_014905
- dbSNP
- rs3732211
- Type
- single nucleotide variant
- Location
- chr2:190953597 (GRCh38)
- Structure
- AlphaFold pLDDT 85.66 · 4 PDB
- Residue 561
- 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.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
- GLS c.1072-2A>C Likely pathogenic ★ 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-ala561 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown