HCK p.Ser45=
c.135C>T · VCV4689116
Benign
Single submitter
Classification
Benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Common
common (popmax 19.1%, afr) — too common for a highly-penetrant pathogenic allele
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 -0.25 | GERP -0.88 |
| Overall | ||
| CADD | 1.484 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
19.1%
African / African-American · 14,308/74,958 alleles
Filtering AF
18.8%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 18.7%
Overall
1.64%
26,404/1,613,998 alleles · common
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 19.1% | 5 |
| Middle Eastern | 2.54% | 39 |
| Remaining individualsnot grpmax-eligible | 2.1% | 48 |
| Finnishnot grpmax-eligible | 1.77% | 56 |
| East Asian | 1.68% | 59 |
| Admixed American | 1.65% | 60 |
| South Asian | 1.62% | 62 |
| European (non-Finnish) | 0.519% | 193 |
| Ashkenazi Jewishnot grpmax-eligible | 0.5% | 200 |
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
- HCK
- Protein
- p.Ser45=
- Coding
- c.135C>T
- MANE Select
- NM_002110
- Type
- single nucleotide variant
- Location
- chr20:32071734 (GRCh38)
- Gene constraint
- LOEUF 0.795 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 83.93 · 42 PDB
Similar variants
- HCK p.Arg123Trp Uncertain significance ★★ ⚠ same type
- HCK p.Glu75Gln Uncertain significance ★★ ⚠ same type
- HCK p.Leu139Val Uncertain significance ★★ ⚠ same type
- HCK p.Ser5Pro Uncertain significance ★★ ⚠ same type
- HCK p.Ala44Thr Benign/Likely benign ★★ same type
- HCK p.Asn64= Benign ★★ same type
- HCK p.Asp231= Benign/Likely benign ★★ same type
- HCK p.Glu110= Likely benign ★★ 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/hck-p-ser45 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown