PKLR p.Phe141=
c.423T>C · rs2525301712 · VCV2018596
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Absent
absent from gnomAD v4.1
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 0.14 | GERP 0.26, phastCons 0.23 |
| Overall | ||
| CADD | 9.142 | PHRED · no single calibrated threshold — expert panels disagree |
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.Phe141=
- Coding
- c.423T>C
- MANE Select
- NM_000298
- dbSNP
- rs2525301712
- Type
- single nucleotide variant
- Location
- chr1:155295521 (GRCh38)
- Gene constraint
- LOEUF 0.901 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 90.75 · 67 PDB
- Residue 141
- a turn
Similar variants
- PKLR p.Phe141Ser 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-phe141 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown