RIN2 p.Phe642=
c.1926C>T · rs532217477 · VCV2146353
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0876%, eas)
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 -11 | GERP -10 |
| Overall | ||
| CADD | 0.657 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0876%
East Asian · 39/44,528 alleles
Filtering AF
0.0658%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0582%
Overall
0.00399%
64/1,604,152 alleles · ultra-rare
exomes 55/1,451,828 · genomes 9/152,324 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.0876% | 1,142 |
| Remaining individualsnot grpmax-eligible | 0.00322% | 31,075 |
| Admixed American | 0.00171% | 58,310 |
| European (non-Finnish) | 0.0017% | 58,777 |
| Finnishnot grpmax-eligible | 0.00158% | 63,340 |
| African / African-American | 0.00133% | 74,918 |
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.Phe642=
- Coding
- c.1926C>T
- MANE Select
- NM_018993
- dbSNP
- rs532217477
- Type
- single nucleotide variant
- Location
- chr20:19990169 (GRCh38)
- Gene constraint
- LOEUF 0.637 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
- Structure
- AlphaFold pLDDT 64.30
- Residue 642
- 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-phe642 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown