Is RIN2 p.Arg632Trp (c.1894C>T) pathogenic?

RIN2 p.Arg632Trp (c.1894C>T) is classified Uncertain significance in RIN2 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-06-29). AlphaMissense: likely benign (0.3297); Very rare (popmax 8.52e-05%, nfe).

How common is RIN2 p.Arg632Trp (c.1894C>T) in the general population?

RIN2 p.Arg632Trp (c.1894C>T) is very rare (popmax 8.52e-05%, nfe) (gnomAD).

What do computational predictors say about RIN2 p.Arg632Trp (c.1894C>T)?

AlphaMissense predicts likely benign (score 0.3297) — an in-silico prediction, not a clinical call.

RIN2 p.Arg632Trp

c.1894C>T · rs865919406 · VCV1980181

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.3297 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.52e-05%, nfe)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.3297	likely benign
REVEL	0.305	indeterminate
SaProt	LLR -12.08	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.21	GERP 3.8, phastCons 0.97
Regional constraint	o/e 0.93	unconstrained · MANE · 241 bp · p 0.45 · regional, not allelic
Overall
CADD	25.9	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.52e-05% European (non-Finnish) · 1/1,173,934 alleles

Overall 6.24e-05% 1/1,601,336 alleles · very rare exomes 1/1,448,976 · genomes 0/152,360 · joint denominator

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.Arg632Trp
Coding: c.1894C>T
MANE Select: NM_018993
dbSNP: rs865919406
Type: single nucleotide variant
Location: chr20:19990137 (GRCh38)
Gene constraint: LOEUF 0.637 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 64.30
Residue 632: the vps9 domain

Full RIN2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

RIN2 p.Arg632Gln Uncertain significance ★ ⚠ same residue
RIN2 p.Arg632= Likely benign same residue
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

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-arg632trp (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown