CLOCK p.Phe233=
c.699T>C · rs34401111 · VCV775979
Benign
Single submitter
Classification
Benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
low-frequency (popmax 4.92%, 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 5.3 | GERP -1.4, phastCons 1 |
| Overall | ||
| CADD | 9.306 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
4.92%
African / African-American · 3,694/75,018 alleles
Filtering AF
4.79%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 4.74%
Overall
0.254%
4,105/1,613,848 alleles · low-frequency
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 4.92% | 20 |
| Remaining individualsnot grpmax-eligible | 0.304% | 329 |
| Admixed American | 0.283% | 353 |
| Middle Eastern | 0.132% | 758 |
| South Asian | 0.011% | 9,108 |
| European (non-Finnish) | 0.0028% | 35,752 |
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
- CLOCK
- Protein
- p.Phe233=
- Coding
- c.699T>C
- MANE Select
- NM_004898
- dbSNP
- rs34401111
- Type
- single nucleotide variant
- Location
- chr4:55458985 (GRCh38)
- Gene constraint
- LOEUF 0.496 · pLI 0.97 (gnomAD)
- Structure
- AlphaFold pLDDT 61.90 · 2 PDB
Similar variants
- CLOCK c.674-10A>G Benign ★★ same type
- CLOCK p.Ala34= Benign ★★ same type
- CLOCK p.Gly235Glu Likely benign ★★ same type
- CLOCK c.2362-2A>G Uncertain significance ★ same type
- CLOCK p.Ala432Pro Uncertain significance ★ ⚠ same type
- CLOCK p.Ala691Gly Uncertain significance ★ ⚠ same type
- CLOCK p.Arg242Lys Uncertain significance ★ ⚠ same type
- CLOCK p.Arg386Gln 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/clock-p-phe233 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown