PKLR p.Arg498=
c.1494C>T · VCV4913964
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0169%, mid)
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 -0.03 | GERP -2.8, phastCons 0.19 |
| Overall | ||
| CADD | 12.33 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0169%
Middle Eastern · 1/5,912 alleles
Filtering AF
0.00143%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000891%
Overall
0.00031%
5/1,614,006 alleles · ultra-rare
exomes 5/1,461,662 · genomes 0/152,344 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.0169% | 5,912 |
| South Asian | 0.00439% | 22,768 |
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.Arg498=
- Coding
- c.1494C>T
- MANE Select
- NM_000298
- Type
- single nucleotide variant
- Location
- chr1:155291880 (GRCh38)
- Gene constraint
- LOEUF 0.901 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 90.75 · 67 PDB
- Residue 498
- a UniProt-annotated variant site (in cnsha2); a β-strand
Similar variants
- PKLR p.Arg498Cys Likely pathogenic ★ same residue
- PKLR p.Arg498Ser Likely pathogenic ★ same residue
- PKLR p.Arg498His Conflicting classifications of pathogenicity ★ ⚠ 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
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-arg498 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown