PKLR p.Ser2=
c.6G>A · rs139697646 · VCV292821
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 -4.5 | GERP -3.4 |
| Overall | ||
| CADD | 1.395 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Remaining individualsnot grpmax-eligible | 0.106% | 947 |
| European (non-Finnish)grpmax | 0.0514% | 1,944 |
| African / African-American | 0.00533% | 18,748 |
| Admixed American | 0.00333% | 29,995 |
| East Asian | 0.00223% | 44,872 |
Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.
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
- PKLR
- Protein
- p.Ser2=
- Coding
- c.6G>A
- MANE Select
- NM_000298
- dbSNP
- rs139697646
- Type
- single nucleotide variant
- Location
- chr1:155301390 (GRCh38)
- Gene constraint
- LOEUF 0.901 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 90.75 · 67 PDB
- Residue 2
- a modified residue (phosphoserine)
Disease context
pyruvate kinase deficiency of red cells — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatmentsFor Hemolytic anemia due to red cell pyruvate kinase deficiency (Orphanet):
- Inheritance
- Autosomal recessive
- Onset
- Infancy, Neonatal
- Prevalence
- 1-9 / 100 000 (Specific population)
Similar variants
- PKLR p.Ser2Leu Uncertain significance ★★ ⚠ same residue
- PKLR c.1618+1G>A Likely pathogenic ★★ same condition
- PKLR c.694+2T>G Pathogenic/Likely pathogenic ★★ same condition
- PKLR p.Ala423= Pathogenic/Likely pathogenic ★★ same condition
- PKLR p.Arg270Ter Pathogenic ★★ same condition
- PKLR p.Arg479His Pathogenic ★★ ⚠ same condition
- PKLR p.Arg486Trp Pathogenic/Likely pathogenic ★★ same condition
- PKLR p.Arg488Ter Pathogenic ★★ same condition
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/pklr-p-ser2 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown