C2 c.1455+19A>G
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
very rare (popmax 0.00833%, amr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| Splice region | donor +19 | near-intronic (+19 nt from the splice site) |
|---|---|---|
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP -0.42 | GERP -2.6 |
| Non-coding constraint | Z 6.37 | 1 kb window · o/e 0.58 · regional · uncalibrated |
| Overall | ||
| CADD | 3.543 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00833%
Admixed American · 5/60,002 alleles
Filtering AF
0.00323%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00207%
Overall
0.00112%
18/1,606,808 alleles · very rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.00833% | 12,000 |
| Remaining individualsnot grpmax-eligible | 0.00482% | 20,759 |
| African / African-American | 0.00134% | 74,826 |
| European (non-Finnish) | 0.000766% | 130,483 |
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
- C2
- Coding
- c.1455+19A>G
- MANE Select
- NM_000063
- dbSNP
- rs750135610
- Type
- single nucleotide variant
- Location
- chr6:31943338 (GRCh38)
- Gene constraint
- LOEUF 0.909 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 88.61 · 14 PDB
Similar variants
- C2 c.1902+5G>A Uncertain significance ★★ same type
- C2 c.2029+5G>A Uncertain significance ★★ same type
- C2 p.Ala363Thr Uncertain significance ★★ ⚠ same type
- C2 p.Ala682Glu Uncertain significance ★★ ⚠ same type
- C2 p.Arg124Gln Uncertain significance ★★ ⚠ same type
- C2 p.Arg129His Uncertain significance ★★ ⚠ same type
- C2 p.Arg174Cys Uncertain significance ★★ ⚠ same type
- C2 p.Arg176Cys 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/c2-c-1455-plus-19a-g (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown