CTSA p.Met327Ile
c.981G>A · VCV4847822
Uncertain significance
Single submitter
Classification
Uncertain significance
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
AlphaMissense
ambiguous
0.3889 · ACMG-weighted
gnomAD v4.1
Absent
absent from gnomAD v4.1
Missense predictors
0/2 damaging
REVEL, SaProt · AlphaMissense no call
Computational evidence
| Protein change | ||
| AlphaMissense | 0.3889 | ambiguous |
|---|---|---|
| REVEL | 0.275 | benign-leaning |
| SaProt | LLR -3.52 | tolerated |
| ⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call. | ||
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 5.3 | GERP 1.8, phastCons 1 |
| Regional constraint | o/e 0.85 | unconstrained · MANE · 4,432 bp · p 0.0086 · regional, not allelic |
| Overall | ||
| CADD | 23.3 | 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
- CTSA
- Protein
- p.Met327Ile
- Coding
- c.981G>A
- MANE Select
- NM_000308
- Type
- single nucleotide variant
- Location
- chr20:45895026 (GRCh38)
- Gene constraint
- LOEUF 0.851 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 94.59 · 12 PDB
- Residue 327
- a disulfide bond; a β-strand
Similar variants
- CTSA p.Met327Thr Uncertain significance ★★ ⚠ same residue
- CTSA c.1-2A>G Pathogenic/Likely pathogenic ★★ same type
- CTSA c.358-2A>G Likely pathogenic ★★ same type
- CTSA c.601-2A>G Pathogenic/Likely pathogenic ★★ same type
- CTSA c.692+3A>G Pathogenic ★★ same type
- CTSA c.948+1G>A Likely pathogenic ★★ same type
- CTSA p.Arg375Ter Pathogenic/Likely pathogenic ★★ same type
- CTSA p.Cys256Ter 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/ctsa-p-met327ile (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown