THOC6 p.Pro127=
c.381T>G · rs1596477517 · VCV737853
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
very rare (popmax 0.00267%, afr)
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 -2.5 | GERP -3.4 |
| Overall | ||
| CADD | 1.13 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00267%
African / African-American · 2/74,972 alleles
Filtering AF
0.000543%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000429%
Overall
0.000868%
14/1,612,752 alleles · very rare
exomes 14/1,460,552 · genomes 0/152,200 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.00267% | 37,486 |
| European (non-Finnish) | 0.00102% | 98,239 |
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
- THOC6
- Protein
- p.Pro127=
- Coding
- c.381T>G
- MANE Select
- NM_024339
- dbSNP
- rs1596477517
- Type
- single nucleotide variant
- Location
- chr16:3026383 (GRCh38)
- Gene constraint
- LOEUF 0.872 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 93.63 · 3 PDB
Similar variants
- THOC6 p.Pro127Ser Uncertain significance ★ ⚠ same residue
- THOC6 c.155+1G>T Pathogenic/Likely pathogenic ★★ same type
- THOC6 c.810+1G>A Pathogenic/Likely pathogenic ★★ same type
- THOC6 p.Arg247Ter Pathogenic/Likely pathogenic ★★ same type
- THOC6 p.Arg87Ter Pathogenic ★★ same type
- THOC6 p.Gly190Glu Pathogenic/Likely pathogenic ★★ same type
- THOC6 p.Gly275Asp Pathogenic/Likely pathogenic ★★ ⚠ same type
- THOC6 p.Gly46Arg Likely pathogenic ★★ 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/thoc6-p-pro127 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown