TIMELESS p.Ser63=
c.189C>T · rs369162799 · VCV2643096
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0289%, nfe)
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 -1.1 | GERP -3.1 |
| Overall | ||
| CADD | 5.339 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0289%
European (non-Finnish) · 341/1,180,044 alleles
Filtering AF
0.0264%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0253%
Overall
0.0224%
361/1,614,012 alleles · ultra-rare
exomes 346/1,461,820 · genomes 15/152,192 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.0289% | 3,461 |
| Remaining individualsnot grpmax-eligible | 0.0192% | 5,207 |
| African / African-American | 0.004% | 24,975 |
| Admixed American | 0.00333% | 30,001 |
| South Asian | 0.00329% | 30,360 |
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
- TIMELESS
- Protein
- p.Ser63=
- Coding
- c.189C>T
- MANE Select
- NM_003920
- dbSNP
- rs369162799
- Type
- single nucleotide variant
- Location
- chr12:56433835 (GRCh38)
- Gene constraint
- LOEUF 0.857 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 74.56 · 9 PDB
- Residue 63
- the 'required for homodimerization and for interaction with cry1 and chek1' region; an α-helix
Similar variants
- TIMELESS p.Asn337Ser Uncertain significance ★★ ⚠ same type
- TIMELESS p.Ala1145= Benign/Likely benign ★★ same type
- TIMELESS p.Ala129Ser Benign/Likely benign ★★ same type
- TIMELESS p.Arg905Trp Benign/Likely benign ★★ ⚠ same type
- TIMELESS p.Met578Val Benign ★★ same type
- TIMELESS p.Phe1060Leu Benign ★★ same type
- TIMELESS p.Phe509= Benign ★★ same type
- TIMELESS c.909+5G>A 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/timeless-p-ser63 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown