TTC19 c.519+3A>G
Uncertain significance
Single submitter
Classification
Uncertain significance
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00356%, nfe)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal. | ||
| Splicing | ||
| Splice region | donor +3 | donor splice region (+3, within the first 6 intronic nt) · inside the BP7-excluded zone |
|---|---|---|
| SpliceAI | Δ0.23 | donor loss · deltas |
| Constraint at this position | ||
| Conservation | phyloP 4.2 | GERP 1.7, phastCons 1 |
| Non-coding constraint | Z 0.84 | 1 kb window · o/e 0.94 · regional · uncalibrated |
| Overall | ||
| CADD | 19.3 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00356%
European (non-Finnish) · 42/1,179,766 alleles
Filtering AF
0.00267%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00236%
Overall
0.00266%
43/1,613,586 alleles · very rare
exomes 39/1,461,390 · genomes 4/152,196 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.00356% | 28,090 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,470 |
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
- Coding
- c.519+3A>G
- MANE Select
- NM_017775
- Type
- single nucleotide variant
- Location
- chr17:16003890 (GRCh38)
- Gene constraint
- LOEUF 1.049 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 80.28
Similar variants
- 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
- TTC19 p.Ala200Val 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-c-519-plus-3a-g (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown