PLPBP p.Asp264=
c.792C>T · rs372209680 · VCV2987094
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00267%, afr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.031 | moderately benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP -0.19 | GERP -4.5 |
| Overall | ||
| CADD | 3.297 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00267%
African / African-American · 2/74,920 alleles
Filtering AF
0.000763%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000605%
Overall
0.00118%
19/1,613,528 alleles · very rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.00267% | 37,460 |
| East Asian | 0.00223% | 44,856 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,448 |
| European (non-Finnish) | 0.00127% | 78,645 |
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.Asp264=
- Coding
- c.792C>T
- MANE Select
- NM_007198
- dbSNP
- rs372209680
- Type
- single nucleotide variant
- Location
- chr8:37778068 (GRCh38)
- Gene constraint
- LOEUF 1.049 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 89.49
- Residue 264
- 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 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
- PLPBP p.Arg250Gln Uncertain significance ★★ ⚠ same type
- PLPBP p.Arg63Cys 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-asp264 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown