C6 p.Ala119=
c.357G>A · rs577864970 · VCV2419055
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0187%, sas)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -0.19 | GERP -1.5, phastCons 0.26 |
| Overall | ||
| CADD | 8.488 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0187%
South Asian · 17/91,078 alleles
Filtering AF
0.0118%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00976%
Overall
0.0026%
42/1,613,590 alleles · ultra-rare
exomes 37/1,461,342 · genomes 5/152,248 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.0187% | 5,358 |
| Remaining individualsnot grpmax-eligible | 0.0032% | 31,245 |
| African / African-American | 0.00267% | 37,501 |
| East Asian | 0.00223% | 44,864 |
| Admixed American | 0.00167% | 59,998 |
| European (non-Finnish) | 0.00161% | 62,084 |
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
- C6
- Protein
- p.Ala119=
- Coding
- c.357G>A
- MANE Select
- NM_000065
- dbSNP
- rs577864970
- Type
- single nucleotide variant
- Location
- chr5:41199856 (GRCh38)
- Gene constraint
- LOEUF 1.008 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 79.72 · 11 PDB
- Residue 119
- the tsp type-1 2 domain; a UniProt-annotated variant site (in allotype c6 a)
Similar variants
- C6 p.Ala119Glu Benign/Likely benign ★★ same residue
- C6 p.Arg596Ter Pathogenic/Likely pathogenic ★★ same type
- C6 p.Arg606Ter Pathogenic ★★ same type
- C6 p.Cys218Ter Pathogenic/Likely pathogenic ★★ same type
- C6 p.Tyr683Ter Pathogenic/Likely pathogenic ★★ same type
- C6 p.Ala21Val Uncertain significance ★★ ⚠ same type
- C6 p.Ala396Gly Uncertain significance ★★ ⚠ same type
- C6 p.Ala456Thr 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/c6-p-ala119 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown