PKLR p.Asp390=
c.1170T>C · rs141596564 · VCV2174927
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
very rare (popmax 0.00364%, nfe)
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 -2.6 | GERP -4.3 |
| Overall | ||
| CADD | 0.487 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00364%
European (non-Finnish) · 43/1,180,036 alleles
Filtering AF
0.00275%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00244%
Overall
0.00297%
48/1,614,106 alleles · very rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.00364% | 27,443 |
| Ashkenazi Jewishnot grpmax-eligible | 0.00338% | 29,608 |
| African / African-American | 0.00267% | 37,469 |
| Admixed American | 0.00167% | 60,008 |
| South Asian | 0.0011% | 91,090 |
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.Asp390=
- Coding
- c.1170T>C
- MANE Select
- NM_000298
- dbSNP
- rs141596564
- Type
- single nucleotide variant
- Location
- chr1:155293537 (GRCh38)
- Gene constraint
- LOEUF 0.901 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 90.75 · 67 PDB
- Residue 390
- an α-helix; a UniProt-annotated variant site (in cnsha2; mantova; almost complete inactivation)
Similar variants
- PKLR p.Asp390Asn 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
- 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-asp390 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown