GLA p.Pro114=
c.342T>A · VCV3281498
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00295%, eas)
Conditions
1
Cardiovascular phenotype
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 0.77 | GERP 1.1, phastCons 0.006 |
| Overall | ||
| CADD | 7.964 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00295%
East Asian · 1/33,866 alleles
Filtering AF
3.7e-05%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 1.4e-05%
Overall
0.000273%
3/1,097,579 alleles · very rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.00295% | 33,866 |
| European (non-Finnish) | 0.000223% | 447,525 |
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
- GLA
- Protein
- p.Pro114=
- Coding
- c.342T>A
- MANE Select
- NM_000169
- Type
- single nucleotide variant
- Location
- chrX:101403838 (GRCh38)
- Structure
- AlphaFold pLDDT 94.45 · 31 PDB
- Residue 114
- a β-strand; a UniProt-annotated variant site (in fabryd)
Similar variants
- GLA p.Pro114Leu Uncertain significance ★★ ⚠ same residue
- GLA c.802-2A>T Pathogenic/Likely pathogenic ★★ same condition
- GLA p.Ala143Pro Pathogenic/Likely pathogenic ★★ same condition
- GLA p.Arg112His Pathogenic/Likely pathogenic ★★ ⚠ same condition
- GLA p.Arg112Leu Pathogenic/Likely pathogenic ★★ same condition
- GLA p.Arg301Gln Pathogenic ★★ ⚠ same condition
- GLA p.Arg363Cys Pathogenic/Likely pathogenic ★★ ⚠ same condition
- GLA p.Cys223Arg Pathogenic/Likely pathogenic ★★ same condition
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/gla-p-pro114 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown