Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
low-frequency (popmax 1.72%, afr)
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 -1.3 | GERP -5.6 |
| Overall | ||
| CADD | 6.585 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
1.72%
African / African-American · 1,285/74,758 alleles
Filtering AF
1.64%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 1.61%
Overall
0.092%
1,468/1,594,862 alleles · low-frequency
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 1.72% | 58 |
| Remaining individualsnot grpmax-eligible | 0.126% | 792 |
| Admixed American | 0.109% | 915 |
| Middle Eastern | 0.0834% | 1,199 |
| European (non-Finnish) | 0.00308% | 32,517 |
| South Asian | 0.00227% | 44,003 |
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
- PHB1
- Protein
- p.Leu251=
- Coding
- c.753C>T
- MANE Select
- NM_002634
- dbSNP
- rs2233670
- Type
- single nucleotide variant
- Location
- chr17:49405058 (GRCh38)
- Structure
- AlphaFold pLDDT 89.36 · 6 PDB
Similar variants
- PHB1 c.511-12C>G Benign ★★ same type
- PHB1 p.Ala244Val Uncertain significance ★ ⚠ same type
- PHB1 p.Arg43Gly Uncertain significance ★ same type
- PHB1 p.Arg72Gln Uncertain significance ★ ⚠ same type
- PHB1 p.Arg93Cys Uncertain significance ★ ⚠ same type
- PHB1 p.Asp68Tyr Uncertain significance ★ ⚠ same type
- PHB1 p.Gln264Arg Uncertain significance ★ same type
- PHB1 p.Gly51Glu 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/phb1-p-leu251 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown