TGDS p.Pro319=
c.957T>C · rs141222845 · VCV1575281
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0272%, nfe)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP 1.4 | GERP -0.25, phastCons 1 |
| Overall | ||
| CADD | 7.74 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0272%
European (non-Finnish) · 320/1,175,176 alleles
Filtering AF
0.0247%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0238%
Overall
0.0208%
333/1,603,626 alleles · ultra-rare
exomes 309/1,451,346 · genomes 24/152,280 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.0272% | 3,672 |
| Remaining individualsnot grpmax-eligible | 0.00968% | 10,326 |
| Finnishnot grpmax-eligible | 0.00471% | 21,239 |
| Admixed American | 0.00341% | 29,365 |
| African / African-American | 0.00134% | 74,622 |
| South Asian | 0.00113% | 88,766 |
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
- TGDS
- Protein
- p.Pro319=
- Coding
- c.957T>C
- MANE Select
- NM_014305
- dbSNP
- rs141222845
- Type
- single nucleotide variant
- Location
- chr13:94576339 (GRCh38)
- Gene constraint
- LOEUF 1.184 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 94.42
Similar variants
- TGDS c.313+1G>A Pathogenic/Likely pathogenic ★★ same type
- TGDS p.Ala100Ser Pathogenic/Likely pathogenic ★★ ⚠ same type
- TGDS p.Asn60Lys Uncertain significance ★★ ⚠ same type
- TGDS p.His103Leu Uncertain significance ★★ ⚠ same type
- TGDS p.Leu96Ile Uncertain significance ★★ ⚠ same type
- TGDS p.Val35Ile Uncertain significance ★★ ⚠ same type
- TGDS c.223-73C>T Benign ★★ same type
- TGDS c.313+19T>A Benign/Likely benign ★★ 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/tgds-p-pro319 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown