PKLR p.Ala92Pro
c.274G>C · VCV4741250
Uncertain significance
Single submitter
Classification
Uncertain significance
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
AlphaMissense
likely pathogenic
0.9536 · ACMG-weighted
gnomAD v4.1
Absent
absent from gnomAD v4.1
Missense predictors
2/3 damaging
AlphaMissense, REVEL, SaProt
Computational evidence
| Protein change | ||
| AlphaMissense | 0.9536 | likely pathogenic |
|---|---|---|
| REVEL | 0.76 | pathogenic-leaning |
| SaProt | LLR -8.95 | tolerated |
| ⇒ AlphaMissense and REVEL call this damaging; SaProt does not. | ||
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 2.7 | GERP -2.5, phastCons 0.99 |
| Regional constraint | o/e 0.97 | unconstrained · MANE · 7,868 bp · p 0.44 · regional, not allelic |
| Overall | ||
| CADD | 27.3 | PHRED · no single calibrated threshold — expert panels disagree |
AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.
Population frequency
gnomAD v4.1 · exomes + genomes
Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.
Variant & gene context
- Gene
- PKLR
- Protein
- p.Ala92Pro
- Coding
- c.274G>C
- MANE Select
- NM_000298
- Type
- single nucleotide variant
- Location
- chr1:155300107 (GRCh38)
- Gene constraint
- LOEUF 0.901 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 90.75 · 67 PDB
- Residue 92
- a β-strand
Similar variants
- PKLR p.Ala92Asp Uncertain significance ★ ⚠ same residue
- PKLR c.101-1G>A Pathogenic ★★ same type
- PKLR c.1116+2T>G Pathogenic ★★ same type
- PKLR c.1618+1G>A Likely pathogenic ★★ same type
- PKLR c.694+2T>G Pathogenic/Likely pathogenic ★★ same type
- PKLR p.Ala423= Pathogenic/Likely pathogenic ★★ same type
- PKLR p.Ala495Thr Likely pathogenic ★★ ⚠ same type
- PKLR p.Ala495Val Pathogenic ★★ ⚠ 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/pklr-p-ala92pro (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown