BPHL p.Lys129=
c.387G>A · rs145702455 · VCV2656183
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0988%, 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 2.7 | GERP -0.66, phastCons 1 |
| Overall | ||
| CADD | 5.626 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0988%
European (non-Finnish) · 1,166/1,180,048 alleles
Filtering AF
0.0941%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0921%
Overall
0.0764%
1,234/1,614,274 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.0988% | 1,012 |
| Remaining individualsnot grpmax-eligible | 0.0768% | 1,302 |
| Admixed American | 0.015% | 6,670 |
| African / African-American | 0.00799% | 12,513 |
| Finnishnot grpmax-eligible | 0.00781% | 12,810 |
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
- BPHL
- Protein
- p.Lys129=
- Coding
- c.387G>A
- MANE Select
- NM_004332
- dbSNP
- rs145702455
- Type
- single nucleotide variant
- Location
- chr6:3129053 (GRCh38)
- Gene constraint
- LOEUF 1.262 · pLI <0.01 · ClinGen HI dosage-sensitivity unlikely (gnomAD)
- Structure
- AlphaFold pLDDT 92.43 · 4 PDB
- Residue 129
- the ab hydrolase-1 domain
Similar variants
- TUBB2A p.Thr178Met Pathogenic/Likely pathogenic ★★ same type
- BPHL p.Ala164Pro Uncertain significance ★ ⚠ same type
- BPHL p.Ala164Thr Uncertain significance ★ ⚠ same type
- BPHL p.Ala166Thr Uncertain significance ★ ⚠ same type
- BPHL p.Ala236Ser Uncertain significance ★ ⚠ same type
- BPHL p.Ala252Val Uncertain significance ★ ⚠ same type
- BPHL p.Ala34Ser Uncertain significance ★ ⚠ same type
- BPHL p.Arg12Cys 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/bphl-p-lys129 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown