TTC19 p.Pro253=
c.759G>A · VCV4693030
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0165%, mid)
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 -4.5 | GERP -3.8 |
| Overall | ||
| CADD | 7.871 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0165%
Middle Eastern · 1/6,078 alleles
Filtering AF
0.00106%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000495%
Overall
0.000929%
15/1,613,794 alleles · ultra-rare
exomes 14/1,461,642 · genomes 1/152,152 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.0165% | 6,078 |
| East Asian | 0.00445% | 22,447 |
| African / African-American | 0.00401% | 24,962 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,460 |
| European (non-Finnish) | 0.000678% | 147,483 |
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
- TTC19
- Protein
- p.Pro253=
- Coding
- c.759G>A
- MANE Select
- NM_017775
- Type
- single nucleotide variant
- Location
- chr17:16025099 (GRCh38)
- Gene constraint
- LOEUF 1.049 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 80.28
Similar variants
- TTC19 p.Pro253Leu Conflicting classifications of pathogenicity ★ ⚠ same residue
- TTC19 c.581+1G>C Pathogenic/Likely pathogenic ★★ same type
- TTC19 p.Gln195Ter Pathogenic/Likely pathogenic ★★ same type
- TTC19 p.Leu185Pro Pathogenic/Likely pathogenic ★★ same type
- TTC19 p.Leu219Ter Pathogenic ★★ same type
- TTC19 c.581+4A>C Uncertain significance ★★ same type
- TTC19 c.994+3A>T Uncertain significance ★★ same type
- TTC19 p.Ala122Thr Uncertain significance ★★ ⚠ 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/ttc19-p-pro253 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown