CLOCK p.Ala34=
c.102G>A · rs140319729 · VCV720921
Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
low-frequency (popmax 2.22%, 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 1.9 | GERP -1.2, phastCons 1 |
| Overall | ||
| CADD | 13.15 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
2.22%
African / African-American · 1,666/74,910 alleles
Filtering AF
2.14%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 2.1%
Overall
0.13%
2,098/1,610,084 alleles · low-frequency
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 2.22% | 45 |
| Admixed American | 0.23% | 435 |
| Remaining individualsnot grpmax-eligible | 0.178% | 562 |
| Middle Eastern | 0.149% | 670 |
| European (non-Finnish) | 0.0141% | 7,090 |
| South Asian | 0.0088% | 11,360 |
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
- CLOCK
- Protein
- p.Ala34=
- Coding
- c.102G>A
- MANE Select
- NM_004898
- dbSNP
- rs140319729
- Type
- single nucleotide variant
- Location
- chr4:55479645 (GRCh38)
- Gene constraint
- LOEUF 0.496 · pLI 0.97 (gnomAD)
- Structure
- AlphaFold pLDDT 61.90 · 2 PDB
- Residue 34
- the bhlh domain; an α-helix
Similar variants
- CLOCK c.674-10A>G 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
- CLOCK p.Arg387Gln 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-ala34 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown