TTC19 c.994+71G>A
Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Common
common (popmax 67.3%, 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. | ||
| Splicing | ||
| Splice region | donor +71 | deep intronic (+71 nt into the intron) |
|---|---|---|
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
| Constraint at this position | ||
| Conservation | phyloP -1.8 | GERP -3 |
| Non-coding constraint | Z -0.15 | 1 kb window · o/e 1.01 · regional · uncalibrated |
| Overall | ||
| CADD | 0.109 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
67.3%
African / African-American · 49,561/73,658 alleles
Filtering AF
66.8%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 66.6%
Overall
54.9%
853,931/1,554,794 alleles · common
exomes 765,985/1,402,742 · genomes 87,946/152,052 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 67.3% | 1 |
| Ashkenazi Jewishnot grpmax-eligible | 66.6% | 2 |
| Middle Eastern | 61.9% | 2 |
| Finnishnot grpmax-eligible | 59.4% | 2 |
| European (non-Finnish) | 56.3% | 2 |
| Remaining individualsnot grpmax-eligible | 55.3% | 2 |
| Amishnot grpmax-eligible | 52.3% | 2 |
| Admixed American | 46.8% | 2 |
| South Asian | 43.2% | 2 |
| East Asian | 19% | 5 |
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.994+71G>A
- MANE Select
- NM_017775
- dbSNP
- rs35168566
- Type
- single nucleotide variant
- Location
- chr17:16026773 (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-994-plus-71g-a (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown