C1S p.Gly254=
c.762A>T · rs142481406 · VCV722610
Benign/Likely benign
Multiple submitters
Classification
Benign/Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 4 submitters
gnomAD v4.1
Rare
rare (popmax 0.568%, afr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | all four deltas below 0.2 · A>G here scores Δ0.22 · evaluated, not missing |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP 1.9 | GERP -1.6, phastCons 1 |
| Overall | ||
| CADD | 2.489 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.568%
African / African-American · 426/74,960 alleles
Filtering AF
0.524%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.506%
Overall
0.0343%
554/1,613,378 alleles · rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.568% | 176 |
| Admixed American | 0.0917% | 1,091 |
| Middle Eastern | 0.0825% | 1,212 |
| Remaining individualsnot grpmax-eligible | 0.048% | 2,083 |
| European (non-Finnish) | 0.00322% | 31,038 |
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
- C1S
- Protein
- p.Gly254=
- Coding
- c.762A>T
- MANE Select
- NM_001734
- dbSNP
- rs142481406
- Type
- single nucleotide variant
- Location
- chr12:7065861 (GRCh38)
- Gene constraint
- LOEUF 0.783 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 88.02 · 14 PDB
- Residue 254
- the cub 2 domain; a β-strand
Similar variants
- C1S p.Arg523Ter Pathogenic ★★ same type
- C1S c.1196-3C>T Uncertain significance ★★ same type
- C1S c.717+5G>A Uncertain significance ★★ same type
- C1S c.717+6T>A Uncertain significance ★★ same type
- C1S p.Ala227Val Uncertain significance ★★ ⚠ same type
- C1S p.Ala231Val Uncertain significance ★★ ⚠ same type
- C1S p.Ala584Val Uncertain significance ★★ ⚠ same type
- C1S p.Ala649Thr 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/c1s-p-gly254 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown