RIPPLY2 p.Ser12=
c.36T>C · rs557571290 · VCV2166277
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0233%, afr)
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 1.1 | GERP -2.1 |
| Overall | ||
| CADD | 8.995 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0233%
African / African-American · 17/72,938 alleles
Filtering AF
0.0148%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0122%
Overall
0.00143%
22/1,543,402 alleles · ultra-rare
exomes 13/1,391,218 · genomes 9/152,184 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.0233% | 4,290 |
| Remaining individualsnot grpmax-eligible | 0.00334% | 29,942 |
| Admixed American | 0.00197% | 50,776 |
| European (non-Finnish) | 0.000174% | 573,210 |
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
- RIPPLY2
- Protein
- p.Ser12=
- Coding
- c.36T>C
- MANE Select
- NM_001009994
- dbSNP
- rs557571290
- Type
- single nucleotide variant
- Location
- chr6:83853452 (GRCh38)
- Gene constraint
- LOEUF 1.76 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 62.67
- Residue 12
- the 'disordered' region
Similar variants
- RIPPLY2 p.Ser12fs Uncertain significance ★ same residue
- RIPPLY2 p.Ala14Ser Uncertain significance ★★ ⚠ same type
- RIPPLY2 p.Ala14Thr Uncertain significance ★★ ⚠ same type
- RIPPLY2 p.Ala34Thr Uncertain significance ★★ ⚠ same type
- RIPPLY2 p.Glu118Lys Uncertain significance ★★ ⚠ same type
- RIPPLY2 p.Gly9Cys Uncertain significance ★★ ⚠ same type
- RIPPLY2 p.Met59Thr Uncertain significance ★★ ⚠ same type
- RIPPLY2 c.175-19C>T Likely benign ★★ 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/ripply2-p-ser12 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown