CTSD p.Pro319=
c.957G>A · rs369229897 · VCV205332
Benign/Likely benign
Multiple submitters
Classification
Benign/Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 4 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0515%, eas)
Conditions
2
Inborn genetic diseases
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.013 | strongly benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP -9.7 | |
| Overall | ||
| CADD | 4.756 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0515%
East Asian · 23/44,636 alleles
Filtering AF
0.0352%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0298%
Overall
0.00523%
84/1,606,252 alleles · ultra-rare
exomes 66/1,454,114 · genomes 18/152,138 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.0515% | 1,941 |
| Admixed American | 0.0456% | 2,192 |
| Remaining individualsnot grpmax-eligible | 0.0145% | 6,910 |
| African / African-American | 0.00668% | 14,959 |
| South Asian | 0.00221% | 45,282 |
| European (non-Finnish) | 0.00153% | 65,412 |
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
- CTSD
- Protein
- p.Pro319=
- Coding
- c.957G>A
- MANE Select
- NM_001909
- dbSNP
- rs369229897
- Type
- single nucleotide variant
- Location
- chr11:1754009 (GRCh38)
- Gene constraint
- LOEUF 0.886 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 85.69 · 9 PDB
- Residue 319
- the peptidase a1 domain; a β-strand
Similar variants
- CTSD p.Pro319Leu Uncertain significance ★★ ⚠ same residue
- CTSD c.228+1G>A Likely pathogenic ★★ same condition
- CTSD p.Glu82Ter Pathogenic/Likely pathogenic ★★ same condition
- CTSD c.828-3C>A Uncertain significance ★★ same condition
- CTSD p.Ala10Ser Uncertain significance ★★ ⚠ same condition
- CTSD p.Ala116Thr Uncertain significance ★★ ⚠ same condition
- CTSD p.Ala18Pro Uncertain significance ★★ ⚠ same condition
- CTSD p.Ala18Thr Uncertain significance ★★ ⚠ 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/ctsd-p-pro319 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown