PLPBP p.Pro268=
c.804G>A · rs377626500 · VCV2190808
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0593%, sas)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.013 | strongly benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP -13 | GERP -4.4 |
| Overall | ||
| CADD | 0.033 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0593%
South Asian · 54/91,056 alleles
Filtering AF
0.0466%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0421%
Overall
0.00521%
84/1,613,320 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.0593% | 1,686 |
| East Asian | 0.0156% | 6,405 |
| Remaining individualsnot grpmax-eligible | 0.0112% | 8,921 |
| Admixed American | 0.00167% | 59,996 |
| European (non-Finnish) | 0.00127% | 78,630 |
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.Pro268=
- Coding
- c.804G>A
- MANE Select
- NM_007198
- dbSNP
- rs377626500
- Type
- single nucleotide variant
- Location
- chr8:37778080 (GRCh38)
- Gene constraint
- LOEUF 1.049 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 89.49
- Residue 268
- 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.Pro268Leu 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
- PLPBP p.Arg250Gln 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-pro268 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown