TMC8 p.Ser298=
c.894C>T · rs938539425 · VCV794386
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0329%, mid)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP 2.1 | GERP 0.21, phastCons 0.97 |
| Overall | ||
| CADD | 12.86 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0329%
Middle Eastern · 2/6,084 alleles
Filtering AF
0.0058%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00241%
Overall
0.00031%
5/1,613,930 alleles · ultra-rare
exomes 4/1,461,698 · genomes 1/152,232 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.0329% | 3,042 |
| Admixed American | 0.00167% | 60,008 |
| European (non-Finnish) | 0.000169% | 590,026 |
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
- TMC8
- Protein
- p.Ser298=
- Coding
- c.894C>T
- MANE Select
- NM_152468
- dbSNP
- rs938539425
- Type
- single nucleotide variant
- Location
- chr17:78134471 (GRCh38)
- Gene constraint
- LOEUF 1.201 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
- Structure
- AlphaFold pLDDT 76.77
Similar variants
- TMC8 c.1824-1G>C Pathogenic/Likely pathogenic ★★ same type
- TMC8 c.449-1G>T Likely pathogenic ★★ same type
- TMC8 p.Arg190Ter Pathogenic ★★ same type
- TMC8 p.Ala188Val Uncertain significance ★★ ⚠ same type
- TMC8 p.Ala290Thr Uncertain significance ★★ ⚠ same type
- TMC8 p.Ala313Val Uncertain significance ★★ ⚠ same type
- TMC8 p.Ala316Thr Uncertain significance ★★ ⚠ same type
- TMC8 p.Ala345Thr 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/tmc8-p-ser298 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown