PIGB p.Phe434=
c.1302T>C · rs1253752581 · VCV2807900
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00551%, sas)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -0.69 | GERP -3.4 |
| Overall | ||
| CADD | 2.933 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00551%
South Asian · 5/90,824 alleles
Filtering AF
0.00211%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00137%
Overall
0.000374%
6/1,602,732 alleles · very rare
exomes 6/1,450,424 · genomes 0/152,308 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.00551% | 18,165 |
| Remaining individualsnot grpmax-eligible | 0.00161% | 62,122 |
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
- PIGB
- Protein
- p.Phe434=
- Coding
- c.1302T>C
- MANE Select
- NM_004855
- dbSNP
- rs1253752581
- Type
- single nucleotide variant
- Location
- chr15:55350877 (GRCh38)
- Gene constraint
- LOEUF 1.098 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 88.48
- Residue 434
- a UniProt-annotated variant site (in dee80; uncertain significance)
Similar variants
- PIGB c.795-1G>C Likely pathogenic ★★ same type
- PIGB c.795-2A>G Likely pathogenic ★★ same type
- PIGB c.847-10A>G Pathogenic ★★ same type
- PIGB p.Asp155His Likely pathogenic ★★ same type
- PIGB p.Leu131Ter Pathogenic ★★ same type
- PIGB p.Lys31Ter Pathogenic ★★ same type
- PIGB p.Ala400Thr Uncertain significance ★★ ⚠ same type
- PIGB p.Arg339Trp 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/pigb-p-phe434 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown