GYS2 p.Pro637=
c.1911C>T · VCV3387863
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.000594%, 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 2.7 | GERP -1.1, phastCons 1 |
| Overall | ||
| CADD | 13.13 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.000594%
European (non-Finnish) · 7/1,179,398 alleles
Filtering AF
0.000247%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000159%
Overall
0.000434%
7/1,613,208 alleles · very rare
exomes 3/1,461,094 · genomes 4/152,114 · joint denominator
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
- GYS2
- Protein
- p.Pro637=
- Coding
- c.1911C>T
- MANE Select
- NM_021957
- Type
- single nucleotide variant
- Location
- chr12:21537155 (GRCh38)
- Gene constraint
- LOEUF 1.277 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
- Structure
- AlphaFold pLDDT 87.08
- Residue 637
- the 'disordered' region
Similar variants
- GYS2 c.1062+1G>T Pathogenic/Likely pathogenic ★★ same type
- GYS2 c.1230-1G>A Likely pathogenic ★★ same type
- GYS2 c.1423-1G>A Pathogenic/Likely pathogenic ★★ same type
- GYS2 c.495+1G>T Pathogenic/Likely pathogenic ★★ same type
- GYS2 p.Ala339Pro Pathogenic/Likely pathogenic ★★ same type
- GYS2 p.Arg147Ter Likely pathogenic ★★ same type
- GYS2 p.Arg192Ter Pathogenic/Likely pathogenic ★★ same type
- GYS2 p.Arg246Ter Pathogenic/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/gys2-p-pro637 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown