KHK p.Ser144=
c.432G>A · VCV4954216
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.02%, eas)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -9.2 | GERP -4.7 |
| Overall | ||
| CADD | 0.175 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.02%
East Asian · 9/44,900 alleles
Filtering AF
0.0104%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00779%
Overall
0.00198%
32/1,613,632 alleles · ultra-rare
exomes 26/1,461,428 · genomes 6/152,204 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.02% | 4,989 |
| Admixed American | 0.01% | 10,002 |
| African / African-American | 0.00801% | 12,490 |
| South Asian | 0.00329% | 30,363 |
| Remaining individualsnot grpmax-eligible | 0.0032% | 31,240 |
| Finnishnot grpmax-eligible | 0.00157% | 63,582 |
| European (non-Finnish) | 0.000424% | 236,008 |
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
- KHK
- Protein
- p.Ser144=
- Coding
- c.432G>A
- MANE Select
- NM_006488
- Type
- single nucleotide variant
- Location
- chr2:27097517 (GRCh38)
- Gene constraint
- LOEUF 1.362 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 97.32 · 38 PDB
- Residue 144
- an α-helix
Similar variants
- KHK p.Ser144Leu Uncertain significance ★ ⚠ same residue
- KHK p.Ser144Trp Uncertain significance ★ ⚠ same residue
- KHK p.Ala155Thr Uncertain significance ★★ ⚠ same type
- KHK p.Asn157Thr Uncertain significance ★★ ⚠ same type
- KHK p.Ser273Asn Uncertain significance ★★ ⚠ same type
- KHK p.Thr158Asn Uncertain significance ★★ ⚠ same type
- KHK c.210-328A>G Benign ★★ same type
- KHK c.-245G>A 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/khk-p-ser144 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown