PKLR p.Asp331=
c.993C>T · rs138476691 · VCV724780
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 5 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0657%, 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 -4.6 | GERP -4.3 |
| Overall | ||
| CADD | 0.604 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0657%
Middle Eastern · 4/6,084 alleles
Filtering AF
0.0364%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0351%
Overall
0.0331%
534/1,613,960 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.0657% | 1,521 |
| Remaining individualsnot grpmax-eligible | 0.0496% | 2,016 |
| European (non-Finnish) | 0.0393% | 2,543 |
| Admixed American | 0.0383% | 2,608 |
| African / African-American | 0.00668% | 14,976 |
| South Asian | 0.00659% | 15,181 |
| Ashkenazi Jewishnot grpmax-eligible | 0.00338% | 29,606 |
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.Asp331=
- Coding
- c.993C>T
- MANE Select
- NM_000298
- dbSNP
- rs138476691
- Type
- single nucleotide variant
- Location
- chr1:155294358 (GRCh38)
- Gene constraint
- LOEUF 0.901 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 90.75 · 67 PDB
- Residue 331
- a β-strand; a UniProt-annotated variant site (in cnsha2; parma); a UniProt-annotated variant site (in cnsha2)
Similar variants
- PKLR p.Asp331Asn Likely pathogenic ★★ same residue
- PKLR p.Asp331Glu Pathogenic/Likely pathogenic ★★ ⚠ 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
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-asp331 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown