C8A c.655-4del
Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
low-frequency (popmax 3.53%, afr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| Splice region | acceptor -4 | acceptor splice region (-4, within the last 20 intronic nt) · inside the BP7-excluded zone |
|---|---|---|
| SpliceAI | — | not assessed · substitutions only |
| Constraint at this position | ||
| Conservation | phyloP 0.8 | GERP -0.5 |
| Non-coding constraint | Z 0.94 | 1 kb window · o/e 0.93 · regional · uncalibrated |
| Overall | ||
| CADD | 0.36 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
3.53%
African / African-American · 2,406/68,216 alleles
Filtering AF
3.41%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 3.36%
Overall
0.298%
4,028/1,353,932 alleles · low-frequency
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 3.53% | 28 |
| Remaining individualsnot grpmax-eligible | 0.261% | 383 |
| Admixed American | 0.194% | 516 |
| South Asian | 0.156% | 642 |
| Middle Eastern | 0.149% | 670 |
| European (non-Finnish) | 0.119% | 838 |
| Finnishnot grpmax-eligible | 0.106% | 942 |
| East Asian | 0.0495% | 2,019 |
| Ashkenazi Jewishnot grpmax-eligible | 0.0435% | 2,300 |
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
- C8A
- Coding
- c.655-4del
- MANE Select
- NM_000562
- dbSNP
- rs61482695
- Type
- Deletion
- Location
- chr1:56883468 (GRCh38)
- Gene constraint
- LOEUF 1.168 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 79.58 · 11 PDB
Similar variants
- C8A p.Ala153fs Pathogenic ★ same type
- C8A p.Ala360fs Pathogenic ★ same type
- C8A p.Cys194fs Pathogenic ★ same type
- C8A p.Thr72fs Pathogenic ★ same type
- C8A p.Ser445del Uncertain significance ★ same type
- C8A p.Val240_Lys241del 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/c8a-c-655-minus-4del (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown