TIMCC p.Leu77Val
c.229C>G · rs762894900 · VCV1701380
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00119%, sas)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.018 | moderately benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
| Constraint at this position | ||
| Conservation | phyloP 0.2 | GERP -0.91, phastCons 0.003 |
| Regional constraint | o/e 1.02 | unconstrained · MANE · 4,719 bp · p 0.74 · regional, not allelic |
| Overall | ||
| CADD | 5.876 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00119%
South Asian · 1/83,916 alleles
Overall
6.47e-05%
1/1,546,614 alleles · very rare
exomes 1/1,394,254 · genomes 0/152,360 · joint denominator
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.Leu77Val
- Coding
- c.229C>G
- MANE Select
- NM_001329752
- dbSNP
- rs762894900
- Type
- single nucleotide variant
- Location
- chr2:70301783 (GRCh38)
- Structure
- AlphaFold pLDDT 95.42
- Residue 77
- 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-leu77val (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown