RIN2 p.Val677=
c.2031C>A · rs186712522 · VCV390362
Conflicting classifications of pathogenicity
Conflicting submitters
Classification
Conflicting classifications of pathogenicity
ClinVar
Review
Conflicting submitters ★☆☆☆
ClinVar · 4 submitters
gnomAD v4.1
Rare
rare (popmax 0.208%, amr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal. | ||
| Splicing | ||
| SpliceAI | Δ0.35 | donor gain · deltas |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP 0.54 | GERP 2.6, phastCons 1 |
| Overall | ||
| CADD | 14.04 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.208%
Admixed American · 125/59,994 alleles
Filtering AF
0.179%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.167%
Overall
0.0327%
527/1,613,734 alleles · rare
exomes 470/1,461,380 · genomes 57/152,354 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.208% | 480 |
| Remaining individualsnot grpmax-eligible | 0.0576% | 1,735 |
| European (non-Finnish) | 0.0306% | 3,268 |
| Finnishnot grpmax-eligible | 0.00469% | 21,339 |
| African / African-American | 0.00266% | 37,525 |
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
- RIN2
- Protein
- p.Val677=
- Coding
- c.2031C>A
- MANE Select
- NM_018993
- dbSNP
- rs186712522
- Type
- single nucleotide variant
- Location
- chr20:19990274 (GRCh38)
- Gene constraint
- LOEUF 0.637 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
- Structure
- AlphaFold pLDDT 64.30
- Residue 677
- the vps9 domain
Similar variants
- RIN2 p.Ala205Val Uncertain significance ★★ ⚠ same type
- RIN2 p.Ala72Thr Uncertain significance ★★ ⚠ same type
- RIN2 p.Ala8Thr Uncertain significance ★★ ⚠ same type
- RIN2 p.Arg135Cys Uncertain significance ★★ ⚠ same type
- RIN2 p.Arg170Trp Uncertain significance ★★ ⚠ same type
- RIN2 p.Arg255Thr Uncertain significance ★★ ⚠ same type
- RIN2 p.Arg290Leu Uncertain significance ★★ ⚠ same type
- RIN2 p.Arg303Gln 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/rin2-p-val677 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown