C8A c.171+8A>G
Benign/Likely benign
Multiple submitters
Classification
Benign/Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
rare (popmax 0.786%, afr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| Splice region | donor +8 | near-intronic (+8 nt from the splice site) |
|---|---|---|
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP -0.008 | GERP -1.4 |
| Non-coding constraint | Z -1.12 | 1 kb window · o/e 1.08 · regional · uncalibrated |
| Overall | ||
| CADD | 1.267 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.786%
African / African-American · 589/74,904 alleles
Filtering AF
0.734%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.713%
Overall
0.0423%
680/1,607,492 alleles · rare
exomes 337/1,455,184 · genomes 343/152,308 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.786% | 127 |
| Admixed American | 0.0701% | 1,427 |
| Remaining individualsnot grpmax-eligible | 0.0594% | 1,683 |
| Middle Eastern | 0.0496% | 2,015 |
| South Asian | 0.0044% | 22,732 |
| European (non-Finnish) | 0.000426% | 234,825 |
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.171+8A>G
- MANE Select
- NM_000562
- dbSNP
- rs189841210
- Type
- single nucleotide variant
- Location
- chr1:56867710 (GRCh38)
- Gene constraint
- LOEUF 1.168 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 79.58 · 11 PDB
Similar variants
- C8A p.Arg424Ter Pathogenic ★★ same type
- C8A p.Arg498Ter Pathogenic/Likely pathogenic ★★ same type
- C8A p.Glu466Ter Pathogenic ★★ same type
- C8A p.Tyr210Ter Pathogenic/Likely pathogenic ★★ same type
- C8A p.Tyr384Ter Pathogenic/Likely pathogenic ★★ same type
- C8A p.Arg107Cys Uncertain significance ★★ ⚠ same type
- C8A p.Arg196His Uncertain significance ★★ ⚠ same type
- C8A p.Arg207Gln 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-171-plus-8a-g (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown