C8B c.249+2T>A
Likely pathogenic
Single submitter
Classification
Likely pathogenic
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
Consequence
canonical splice-site (±1/±2)
predicted LoF
gnomAD v4.1
Absent
absent from gnomAD v4.1
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal. | ||
| Consequence | canonical splice-site (±1/±2) | predicted loss-of-function |
|---|---|---|
| Splicing | ||
| Splice region | donor +2 | canonical splice dinucleotide (donor +2) · inside the BP7-excluded zone |
| SpliceAI | Δ0.62 | donor loss, 2 bp away · masked 0 · deltas |
| Pangolin | Δ0.78 | loss · gain 0.01 · agrees with SpliceAI · independent |
| Constraint at this position | ||
| Conservation | phyloP 8.9 | GERP 2.2, phastCons 1 |
| Non-coding constraint | Z 0.16 | 1 kb window · o/e 0.99 · regional · uncalibrated |
| Overall | ||
| CADD | 27.2 | PHRED · no single calibrated threshold — expert panels disagree |
Predicted loss-of-function is descriptive, not an applied PVS1 code.
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
- C8B
- Coding
- c.249+2T>A
- MANE Select
- NM_000066
- dbSNP
- rs2522795281
- Type
- single nucleotide variant
- Location
- chr1:56960018 (GRCh38)
- Gene constraint
- LOEUF 1.18 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 81.99 · 8 PDB
Similar variants
- C8B p.Arg284Ter Pathogenic ★★ same type
- C8B p.Arg428Ter Pathogenic ★★ same type
- C8B p.Cys508Ter Pathogenic/Likely pathogenic ★★ same type
- C8B p.Gln91Ter Pathogenic/Likely pathogenic ★★ same type
- C8B p.Trp9Ter Pathogenic ★★ same type
- C8B p.Ala21Thr Uncertain significance ★★ ⚠ same type
- C8B p.Ala446Val Uncertain significance ★★ ⚠ same type
- C8B p.Ala461Ser 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/c8b-c-249-plus-2t-a (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown