PFKL p.Pro329=
c.987T>G · rs147090120 · VCV3043307
Likely benign
No assertion criteria
Classification
Likely benign
ClinVar
Review
No assertion criteria ☆☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0735%, nfe)
Conditions
1
PFKL-related disorder
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 -20 | GERP -3.9 |
| Overall | ||
| CADD | 0.122 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0735%
European (non-Finnish) · 849/1,155,836 alleles
Filtering AF
0.0694%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0676%
Overall
0.0602%
949/1,576,564 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.0735% | 1,361 |
| Finnishnot grpmax-eligible | 0.0657% | 1,522 |
| Remaining individualsnot grpmax-eligible | 0.0396% | 2,528 |
| South Asian | 0.0272% | 3,676 |
| Middle Eastern | 0.017% | 5,892 |
| African / African-American | 0.00951% | 10,519 |
| Admixed American | 0.00518% | 19,295 |
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
- PFKL
- Protein
- p.Pro329=
- Coding
- c.987T>G
- MANE Select
- NM_002626
- dbSNP
- rs147090120
- Type
- single nucleotide variant
- Location
- chr21:44318520 (GRCh38)
- Gene constraint
- LOEUF 1.028 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 92.53 · 5 PDB
- Residue 329
- the 'n-terminal catalytic pfk domain 1' region
Disease context
PFKL-related disorder
Similar variants
- PFKL c.1410-5T>C Likely benign same condition
- PFKL c.86-818C>T Benign same condition
- PFKL p.Ala417= Likely benign same condition
- PFKL p.Arg151= Likely benign same condition
- PFKL p.Asn531= Likely benign same condition
- PFKL p.Asp705Glu Likely benign same condition
- PFKL p.Tyr761= Likely benign same condition
- PFKL p.Arg513Cys Uncertain significance ★★ ⚠ 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/pfkl-p-pro329 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown