TTC19 p.Leu125=
c.375C>T · rs149339696 · VCV515987
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0637%, sas)
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 -0.71 | GERP -1.8, phastCons 0.025 |
| Overall | ||
| CADD | 10.73 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0637%
South Asian · 58/91,076 alleles
Filtering AF
0.0505%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0458%
Overall
0.00614%
99/1,613,352 alleles · ultra-rare
exomes 87/1,461,074 · genomes 12/152,278 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.0637% | 1,570 |
| Middle Eastern | 0.033% | 3,031 |
| Remaining individualsnot grpmax-eligible | 0.0096% | 10,417 |
| African / African-American | 0.00267% | 37,519 |
| European (non-Finnish) | 0.00263% | 38,064 |
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.Leu125=
- Coding
- c.375C>T
- MANE Select
- NM_017775
- dbSNP
- rs149339696
- Type
- single nucleotide variant
- Location
- chr17:16001977 (GRCh38)
- Gene constraint
- LOEUF 1.049 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 80.28
Similar variants
- TTC19 p.Leu125Val Uncertain significance ★ ⚠ 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-leu125 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown