TTC19 c.-347C>A
Benign/Likely benign
Multiple submitters
Classification
Benign/Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Common
common (popmax 11.4%, afr) — too common for a highly-penetrant pathogenic allele
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.093 | moderately benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP -0.64 | GERP 0.46 |
| Non-coding constraint | Z 3.07 | 1 kb window · o/e 0.79 · regional · uncalibrated |
| Overall | ||
| CADD | 8.513 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
11.4%
African / African-American · 8,525/74,896 alleles
Filtering AF
11.2%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 11.1%
Overall
0.619%
9,890/1,596,822 alleles · common
exomes 4,990/1,444,514 · genomes 4,900/152,308 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 11.4% | 9 |
| Remaining individualsnot grpmax-eligible | 0.908% | 110 |
| Admixed American | 0.788% | 127 |
| Middle Eastern | 0.565% | 177 |
| European (non-Finnish) | 0.0235% | 4,252 |
| South Asian | 0.0232% | 4,311 |
| Ashkenazi Jewishnot grpmax-eligible | 0.00678% | 14,743 |
| Finnishnot grpmax-eligible | 0.00194% | 51,482 |
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.-347C>A
- MANE Select
- NM_017775
- dbSNP
- rs60636875
- Type
- single nucleotide variant
- Location
- chr17:15999502 (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-minus-347c-a (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown