GLA p.Thr141Pro
c.421A>C · VCV4081423
Likely pathogenic
Single submitter
Classification
Likely pathogenic
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
AlphaMissense
likely pathogenic
0.84 · ACMG-weighted
gnomAD v4.1
Absent
absent from gnomAD v4.1
Missense predictors
3/3 damaging
AlphaMissense, REVEL, SaProt
Computational evidence
| Protein change | ||
| AlphaMissense | 0.84 | likely pathogenic ✓ concordant with ClinVar |
|---|---|---|
| REVEL | 0.968 | strongly pathogenic-leaning |
| SaProt | LLR -11.70 | damaging |
| ⇒ AlphaMissense, REVEL and SaProt all call this damaging. | ||
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 7.8 | GERP 3.4, phastCons 1 |
| Regional constraint | o/e 0.66 | unconstrained · MANE · 6,067 bp · p 6.6e-08 · regional, not allelic |
| Overall | ||
| CADD | 26.6 | PHRED · no single calibrated threshold — expert panels disagree |
AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.
Population frequency
gnomAD v4.1 · exomes + genomes
Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.
Variant & gene context
- Gene
- GLA
- Protein
- p.Thr141Pro
- Coding
- c.421A>C
- MANE Select
- NM_000169
- Type
- single nucleotide variant
- Location
- chrX:101401758 (GRCh38)
- Structure
- AlphaFold pLDDT 94.45 · 31 PDB
Similar variants
- GLA p.Thr141Ile Pathogenic/Likely pathogenic ★★ same residue
- GLA p.Thr141Asn Likely pathogenic ★ same residue
- GLA p.Thr141fs Pathogenic ★ same residue
- GLA c.1000-10G>A Likely pathogenic ★★ same type
- GLA c.1000-1G>A Pathogenic ★★ same type
- GLA c.1000-1G>C Pathogenic ★★ same type
- GLA c.1023A>C Pathogenic/Likely pathogenic ★★ ⚠ same type
- GLA c.194+1G>A 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/gla-p-thr141pro (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown