RIN2 p.Ser728=
c.2184G>A · rs754028614 · VCV1667268
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0332%, mid)
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 -11 | GERP -15 |
| Overall | ||
| CADD | 0.212 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0332%
Middle Eastern · 2/6,022 alleles
Filtering AF
0.00585%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00384%
Overall
0.00497%
78/1,568,826 alleles · ultra-rare
exomes 74/1,416,620 · genomes 4/152,206 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.0332% | 3,011 |
| Finnishnot grpmax-eligible | 0.0178% | 5,610 |
| Remaining individualsnot grpmax-eligible | 0.0115% | 8,710 |
| African / African-American | 0.0108% | 9,262 |
| South Asian | 0.00588% | 17,009 |
| Admixed American | 0.00382% | 26,173 |
| European (non-Finnish) | 0.00355% | 28,190 |
| Ashkenazi Jewishnot grpmax-eligible | 0.00347% | 28,800 |
| East Asian | 0.00232% | 43,138 |
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.Ser728=
- Coding
- c.2184G>A
- MANE Select
- NM_018993
- dbSNP
- rs754028614
- Type
- single nucleotide variant
- Location
- chr20:19992283 (GRCh38)
- Gene constraint
- LOEUF 0.637 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
- Structure
- AlphaFold pLDDT 64.30
- Residue 728
- 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-ser728 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown