BBS7 p.Asp421Asn
c.1261G>A · VCV4968383
Uncertain significance
Single submitter
Classification
Uncertain significance
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
AlphaMissense
likely benign
0.1182 · ACMG-weighted
gnomAD v4.1
Absent
absent from gnomAD v4.1
Missense predictors
1/2 damaging
AlphaMissense, SaProt · REVEL no call
Computational evidence
| Protein change | ||
| AlphaMissense | 0.1182 | likely benign |
|---|---|---|
| REVEL | 0.419 | indeterminate |
| SaProt | LLR -11.28 | damaging |
| ⇒ SaProt calls this damaging; AlphaMissense does not; REVEL makes no call. | ||
| Splicing | ||
| SpliceAI | Δ0.22 | donor loss, 44 bp away · masked 0 · deltas |
| Pangolin | Δ0.30 | loss · gain 0.04 · agrees with SpliceAI · independent |
| Constraint at this position | ||
| Conservation | phyloP 7.6 | GERP 1.8, phastCons 1 |
| Regional constraint | o/e 0.87 | unconstrained · MANE · 44 kb · p 0.00015 · regional, not allelic |
| Overall | ||
| CADD | 26.5 | PHRED · no single calibrated threshold — expert panels disagree |
AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.
Population frequency
gnomAD v4.1 · exomes + genomes
Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.
Variant & gene context
- Gene
- BBS7
- Protein
- p.Asp421Asn
- Coding
- c.1261G>A
- MANE Select
- NM_176824
- Type
- single nucleotide variant
- Location
- chr4:121843971 (GRCh38)
- Gene constraint
- LOEUF 0.701 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
- Structure
- AlphaFold pLDDT 92.99
Similar variants
- BBS7 p.Asp421Glu Conflicting classifications of pathogenicity ★ ⚠ same residue
- BBS7 p.Asp421= Likely benign ★ same residue
- BBS7 c.1305+2T>A Likely pathogenic ★★ same type
- BBS7 c.1371+1G>A Likely pathogenic ★★ same type
- BBS7 c.1512-1G>A Likely pathogenic ★★ same type
- BBS7 c.1677-2A>G Pathogenic/Likely pathogenic ★★ same type
- BBS7 c.1891-2A>C Pathogenic/Likely pathogenic ★★ same type
- BBS7 c.342-2A>G Pathogenic/Likely pathogenic ★★ 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/bbs7-p-asp421asn (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown