C1QB p.Ala199=
c.597C>T · rs143834228 · VCV799514
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0667%, amr)
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 0.084 | GERP -2.2 |
| Overall | ||
| CADD | 5.385 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0667%
Admixed American · 40/59,998 alleles
Filtering AF
0.0503%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0446%
Overall
0.0118%
190/1,613,434 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.0667% | 1,500 |
| Finnishnot grpmax-eligible | 0.05% | 2,001 |
| Ashkenazi Jewishnot grpmax-eligible | 0.0169% | 5,921 |
| Remaining individualsnot grpmax-eligible | 0.0112% | 8,925 |
| European (non-Finnish) | 0.00899% | 11,128 |
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
- C1QB
- Protein
- p.Ala199=
- Coding
- c.597C>T
- MANE Select
- NM_001378156
- dbSNP
- rs143834228
- Type
- single nucleotide variant
- Location
- chr1:22661227 (GRCh38)
- Gene constraint
- LOEUF 1.001 · pLI 0.25 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
- Structure
- AlphaFold pLDDT 79.87 · 11 PDB
- Residue 199
- the c1q domain; a β-strand; a binding site
Similar variants
- C1QB p.Arg175Ter Likely pathogenic ★★ same type
- C1QB p.Ala121Thr Uncertain significance ★★ ⚠ same type
- C1QB p.Ala124Asp Uncertain significance ★★ ⚠ same type
- C1QB p.Arg134Gln Uncertain significance ★★ ⚠ same type
- C1QB p.Arg134Trp Uncertain significance ★★ ⚠ same type
- C1QB p.Arg186Gln Uncertain significance ★★ ⚠ same type
- C1QB p.Asp21Asn Uncertain significance ★★ ⚠ same type
- C1QB p.Asp226Glu 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/c1qb-p-ala199 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown