C8A p.His465=
c.1395C>T · rs201408238 · VCV1656035
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0165%, mid)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -11 | GERP -4.3 |
| Overall | ||
| CADD | 0.133 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0165%
Middle Eastern · 1/6,056 alleles
Filtering AF
0.00428%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00295%
Overall
0.00322%
52/1,614,170 alleles · ultra-rare
exomes 37/1,461,838 · genomes 15/152,332 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.0165% | 6,056 |
| Admixed American | 0.01% | 10,004 |
| Ashkenazi Jewishnot grpmax-eligible | 0.00676% | 14,803 |
| African / African-American | 0.00666% | 15,013 |
| East Asian | 0.00446% | 22,441 |
| European (non-Finnish) | 0.0028% | 35,758 |
| South Asian | 0.0022% | 45,543 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,510 |
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
- Protein
- p.His465=
- Coding
- c.1395C>T
- MANE Select
- NM_000562
- dbSNP
- rs201408238
- Type
- single nucleotide variant
- Location
- chr1:56912417 (GRCh38)
- Gene constraint
- LOEUF 1.168 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 79.58 · 11 PDB
- Residue 465
- a UniProt-annotated variant site (in c8d1); the macpf domain; an α-helix
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-p-his465 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown