AK1 p.Ser45=
c.135C>T · VCV4683433
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
rare (popmax 0.148%, mid)
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 -4.2 | GERP -4.6 |
| Overall | ||
| CADD | 0.99 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.148%
Middle Eastern · 9/6,062 alleles
Filtering AF
0.0774%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0578%
Overall
0.0218%
352/1,614,132 alleles · rare
exomes 312/1,461,840 · genomes 40/152,292 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.148% | 674 |
| Admixed American | 0.0566% | 1,766 |
| Remaining individualsnot grpmax-eligible | 0.056% | 1,786 |
| European (non-Finnish) | 0.0225% | 4,453 |
| African / African-American | 0.00933% | 10,720 |
| Finnishnot grpmax-eligible | 0.00156% | 63,990 |
| South Asian | 0.0011% | 91,084 |
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
- AK1
- Protein
- p.Ser45=
- Coding
- c.135C>T
- MANE Select
- NM_000476
- Type
- single nucleotide variant
- Location
- chr9:127872762 (GRCh38)
- Gene constraint
- LOEUF 0.873 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 95.82 · 5 PDB
- Residue 45
- the 'nmp' region; an α-helix
Similar variants
- AK1 p.Arg107Ter Pathogenic/Likely pathogenic ★★ same type
- AK1 p.Arg77Gln Uncertain significance ★★ ⚠ same type
- AK1 p.Arg77Trp Uncertain significance ★★ same type
- AK1 p.Glu26Asp Uncertain significance ★★ ⚠ same type
- AK1 p.Gly137Arg Uncertain significance ★★ ⚠ same type
- AK1 p.Gly177Asp Uncertain significance ★★ ⚠ same type
- AK1 p.Ile169Thr Uncertain significance ★★ same type
- AK1 p.Met80Val 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/ak1-p-ser45 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown