BBS2 p.His248=
c.744T>C · rs186893286 · VCV319864
Conflicting classifications of pathogenicity
Conflicting submitters
Classification
Conflicting classifications of pathogenicity
ClinVar
Review
Conflicting submitters ★☆☆☆
ClinVar · 5 submitters
gnomAD v4.1
Rare
rare (popmax 0.582%, eas)
Conditions
3
inherited retinal dystrophy
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 2.3 | GERP 0.75, phastCons 1 |
| Overall | ||
| CADD | 7.915 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.582%
East Asian · 261/44,872 alleles
Filtering AF
0.524%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.501%
Overall
0.0163%
263/1,614,090 alleles · rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.582% | 172 |
| Remaining individualsnot grpmax-eligible | 0.0032% | 31,255 |
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
- BBS2
- Protein
- p.His248=
- Coding
- c.744T>C
- MANE Select
- NM_031885
- dbSNP
- rs186893286
- Type
- single nucleotide variant
- Location
- chr16:56506010 (GRCh38)
- Gene constraint
- LOEUF 0.892 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 89.49
Similar variants
- BBS2 p.His248Leu Uncertain significance ★ ⚠ same residue
- BBS2 c.118-1G>T Likely pathogenic ★★ same condition
- BBS2 c.118-2A>C Likely pathogenic ★★ same condition
- BBS2 c.118-2A>G Likely pathogenic ★★ same condition
- BBS2 c.1225+2T>C Likely pathogenic ★★ same condition
- BBS2 c.1225+2T>G Likely pathogenic ★★ same condition
- BBS2 c.1397+1G>A Pathogenic/Likely pathogenic ★★ same condition
- BBS2 c.1397+2T>C Likely pathogenic ★★ same condition
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/bbs2-p-his248 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown