RIPPLY2 p.Ala29=
c.87G>C · VCV4705978
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.011%, afr)
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 -1 | GERP -4.1 |
| Overall | ||
| CADD | 4.098 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.011%
African / African-American · 8/72,674 alleles
Filtering AF
0.00542%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00391%
Overall
0.000585%
9/1,538,452 alleles · ultra-rare
exomes 4/1,386,256 · genomes 5/152,196 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.011% | 9,084 |
| Remaining individualsnot grpmax-eligible | 0.00168% | 59,658 |
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.Ala29=
- Coding
- c.87G>C
- MANE Select
- NM_001009994
- Type
- single nucleotide variant
- Location
- chr6:83853503 (GRCh38)
- Gene constraint
- LOEUF 1.76 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 62.67
- Residue 29
- the 'disordered' region
Similar variants
- 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
- RIPPLY2 p.Ala4= 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-ala29 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown