TIMCC p.Trp119Ser
c.356G>C · rs552744004 · VCV3035381
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
rare (popmax 0.939%, afr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.004 | strongly benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP -0.9 | GERP -2.7 |
| Regional constraint | o/e 1.02 | unconstrained · MANE · 4,719 bp · p 0.74 · regional, not allelic |
| Overall | ||
| CADD | 1.932 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.939%
African / African-American · 687/73,174 alleles
Filtering AF
0.881%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.857%
Overall
0.053%
814/1,535,386 alleles · rare
exomes 381/1,383,030 · genomes 433/152,356 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.939% | 107 |
| Middle Eastern | 0.218% | 460 |
| Admixed American | 0.0902% | 1,108 |
| Remaining individualsnot grpmax-eligible | 0.08% | 1,250 |
| South Asian | 0.00476% | 21,001 |
| European (non-Finnish) | 0.0014% | 71,652 |
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
- TIMCC
- Protein
- p.Trp119Ser
- Coding
- c.356G>C
- MANE Select
- NM_001329752
- dbSNP
- rs552744004
- Type
- single nucleotide variant
- Location
- chr2:70301656 (GRCh38)
- Structure
- AlphaFold pLDDT 95.42
- Residue 119
- a UniProt-annotated variant site (found in patients with meniere disease; uncertain significance; reduced mrna expression; mislocalization to the cytosol)
Similar variants
- TIMCC p.Asn24= Benign/Likely benign ★★ same type
- FAM136A p.Gln183Ter Pathogenic ★ same type
- FAM136A p.Ala12Val Uncertain significance ★ ⚠ same type
- FAM136A p.Ala144Thr Uncertain significance ★ same type
- FAM136A p.Ala203Asp Uncertain significance ★ ⚠ same type
- FAM136A p.Ala2Val Uncertain significance ★ ⚠ same type
- FAM136A p.Arg163Gly Uncertain significance ★ ⚠ same type
- FAM136A p.Gln10His 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/timcc-p-trp119ser (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown