PHB2 p.Ser293=
c.879C>T · rs376132821 · VCV712104
Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
low-frequency (popmax 1.61%, sas)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.011 | strongly benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 1.6 | GERP 0.92, phastCons 1 |
| Overall | ||
| CADD | 11.82 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
1.61%
South Asian · 1,461/90,836 alleles
Filtering AF
1.54%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 1.51%
Overall
0.0957%
1,542/1,611,314 alleles · low-frequency
exomes 1,448/1,459,192 · genomes 94/152,122 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 1.61% | 62 |
| Remaining individualsnot grpmax-eligible | 0.114% | 879 |
| Middle Eastern | 0.0331% | 3,024 |
| East Asian | 0.00446% | 22,418 |
| African / African-American | 0.00401% | 24,957 |
| Admixed American | 0.00167% | 59,906 |
| European (non-Finnish) | 0.00017% | 588,998 |
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
- PHB2
- Protein
- p.Ser293=
- Coding
- c.879C>T
- MANE Select
- NM_001144831
- dbSNP
- rs376132821
- Type
- single nucleotide variant
- Location
- chr12:6965706 (GRCh38)
- Gene constraint
- LOEUF 0.648 · pLI 0.17 (gnomAD)
- Structure
- AlphaFold pLDDT 85.36 · 8 PDB
Similar variants
- PHB2 p.Thr274= Benign ★★ same type
- PHB2 p.Ala22Val Uncertain significance ★ ⚠ same type
- PHB2 p.Ala33Val Uncertain significance ★ ⚠ same type
- PHB2 p.Arg123Cys Uncertain significance ★ ⚠ same type
- PHB2 p.Arg123His Uncertain significance ★ ⚠ same type
- PHB2 p.Arg191Gln Uncertain significance ★ ⚠ same type
- PHB2 p.Arg209Gln Uncertain significance ★ ⚠ same type
- PHB2 p.Arg222Gln 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/phb2-p-ser293 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown