Is RIN2 p.Arg632= (c.1896G>A) pathogenic?

RIN2 p.Arg632= (c.1896G>A) is classified Likely benign in RIN2 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-05-28). Ultra-rare (popmax 0.0165%, mid); Associated with RIN2-related disorder.

What condition is associated with RIN2 p.Arg632= (c.1896G>A)?

RIN2 p.Arg632= (c.1896G>A) is associated with RIN2-related disorder (ClinVar).

How common is RIN2 p.Arg632= (c.1896G>A) in the general population?

RIN2 p.Arg632= (c.1896G>A) is ultra-rare (popmax 0.0165%, mid) (gnomAD).

RIN2 p.Arg632=

c.1896G>A · rs2515599936 · VCV3039394

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0165%, mid)

Conditions

RIN2-related disorder

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 0.97	GERP 2.7, phastCons 1
Overall
CADD	6.57	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0165% Middle Eastern · 1/6,060 alleles

Overall 0.000125% 2/1,602,328 alleles · ultra-rare exomes 2/1,449,970 · genomes 0/152,358 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0165%	6,060
Remaining individualsnot grpmax-eligible	0.00161%	62,098

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.Arg632=
Coding: c.1896G>A
MANE Select: NM_018993
dbSNP: rs2515599936
Type: single nucleotide variant
Location: chr20:19990139 (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

Disease context

RIN2-related disorder

Similar variants

RIN2 p.Arg632Gln Uncertain significance ★ ⚠ same residue
RIN2 p.Arg632Trp Uncertain significance ★ ⚠ same residue
RIN2 p.Arg14Ter Conflicting classifications of pathogenicity ★ same condition
RIN2 c.351+2T>A Likely pathogenic same condition
RIN2 p.Asn341Ser Uncertain significance ⚠ same condition
RIN2 c.-36-2899G>A Likely benign same condition
RIN2 p.Ala315= Likely benign same condition
RIN2 p.His250= Likely benign same condition

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-arg632 (accessed [today's date]).

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