TIMELESS p.Phe509=
c.1527C>T · rs61752460 · VCV789810
Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
low-frequency (popmax 4.23%, 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 4.5 | GERP 0.3, phastCons 1 |
| Overall | ||
| CADD | 8.751 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
4.23%
African / African-American · 3,171/74,988 alleles
Filtering AF
4.11%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 4.06%
Overall
0.276%
4,453/1,612,584 alleles · low-frequency
exomes 2,493/1,460,308 · genomes 1,960/152,276 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 4.23% | 24 |
| Ashkenazi Jewishnot grpmax-eligible | 1.25% | 80 |
| Remaining individualsnot grpmax-eligible | 0.423% | 236 |
| Admixed American | 0.404% | 248 |
| Middle Eastern | 0.314% | 319 |
| European (non-Finnish) | 0.0325% | 3,078 |
| South Asian | 0.0033% | 30,334 |
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.Phe509=
- Coding
- c.1527C>T
- MANE Select
- NM_003920
- dbSNP
- rs61752460
- Type
- single nucleotide variant
- Location
- chr12:56428287 (GRCh38)
- Gene constraint
- LOEUF 0.857 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 74.56 · 9 PDB
- Residue 509
- 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 c.909+5G>A Uncertain significance ★ same type
- TIMELESS p.Ala1041Gly 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-phe509 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown