CLOCK p.Asp528=
c.1584C>T · rs34812164 · VCV711412
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
rare (popmax 0.361%, 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 2.6 | GERP 1.9, phastCons 1 |
| Overall | ||
| CADD | 7.129 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.361%
European (non-Finnish) · 4,262/1,179,996 alleles
Filtering AF
0.352%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.348%
Overall
0.285%
4,602/1,613,998 alleles · rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.361% | 277 |
| Remaining individualsnot grpmax-eligible | 0.302% | 331 |
| Admixed American | 0.102% | 984 |
| African / African-American | 0.0693% | 1,442 |
| Finnishnot grpmax-eligible | 0.05% | 2,000 |
| Middle Eastern | 0.0495% | 2,021 |
| East Asian | 0.00223% | 44,846 |
| South Asian | 0.0022% | 45,538 |
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.Asp528=
- Coding
- c.1584C>T
- MANE Select
- NM_004898
- dbSNP
- rs34812164
- Type
- single nucleotide variant
- Location
- chr4:55444741 (GRCh38)
- Gene constraint
- LOEUF 0.496 · pLI 0.97 (gnomAD)
- Structure
- AlphaFold pLDDT 61.90 · 2 PDB
- Residue 528
- the 'interaction with nr3c1' region; the 'interaction with sirt1' region; the 'implicated in the circadian rhythmicity' region
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-asp528 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown