PLPBP p.Pro258=
c.774G>A · rs765390963 · VCV2969781
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00534%, afr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.005 | strongly benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP -1.2 | GERP -5.3 |
| Overall | ||
| CADD | 5.707 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00534%
African / African-American · 4/74,908 alleles
Filtering AF
0.00175%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00104%
Overall
0.000744%
12/1,613,612 alleles · very rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.00534% | 18,727 |
| Admixed American | 0.00167% | 59,988 |
| European (non-Finnish) | 0.000593% | 168,535 |
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
- PLPBP
- Protein
- p.Pro258=
- Coding
- c.774G>A
- MANE Select
- NM_007198
- dbSNP
- rs765390963
- Type
- single nucleotide variant
- Location
- chr8:37778050 (GRCh38)
- Gene constraint
- LOEUF 1.049 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 89.49
- Residue 258
- the 'disordered' region; a UniProt-annotated variant site (in epeo1); a UniProt-annotated variant site (in epeo1; decreased expression at the mrna level; undetectable at the protein level in patient's fibroblasts)
Similar variants
- PLPBP p.Pro258Leu Conflicting classifications of pathogenicity ★ ⚠ same residue
- PLPBP p.Pro258fs Uncertain significance ★★ same residue
- PLPBP c.207+1G>T Pathogenic/Likely pathogenic ★★ same type
- PLPBP c.320-2A>G Pathogenic ★★ same type
- PLPBP p.Arg241Gln Pathogenic/Likely pathogenic ★★ same type
- PLPBP p.Pro87Leu Pathogenic/Likely pathogenic ★★ ⚠ same type
- PLPBP p.Ala232= Uncertain significance ★★ same type
- PLPBP p.Arg205Trp 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/plpbp-p-pro258 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown