C8A p.Arg111=
c.333C>T · rs199746178 · VCV1674699
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0982%, eas)
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 -0.059 | GERP -3.4, phastCons 0.67 |
| Overall | ||
| CADD | 9.339 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0982%
East Asian · 44/44,786 alleles
Filtering AF
0.0751%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.067%
Overall
0.00291%
47/1,613,696 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.0982% | 1,018 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,480 |
| South Asian | 0.0011% | 91,066 |
| European (non-Finnish) | 8.48e-05% | 1,179,812 |
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.Arg111=
- Coding
- c.333C>T
- MANE Select
- NM_000562
- dbSNP
- rs199746178
- Type
- single nucleotide variant
- Location
- chr1:56876078 (GRCh38)
- Gene constraint
- LOEUF 1.168 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 79.58 · 11 PDB
- Residue 111
- a disulfide bond; an α-helix; the ldl-receptor class a domain
Similar variants
- C8A p.Arg111Cys Uncertain significance ★ same residue
- C8A p.Arg111His Uncertain significance ★ ⚠ same residue
- 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
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-arg111 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown