Is RIN2 p.Arg89Gly (c.265C>G) pathogenic?

RIN2 p.Arg89Gly (c.265C>G) is classified Uncertain significance in RIN2 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-12-28). AlphaMissense: likely pathogenic (0.8679); Very rare (popmax 0.00168%, amr).

How common is RIN2 p.Arg89Gly (c.265C>G) in the general population?

RIN2 p.Arg89Gly (c.265C>G) is very rare (popmax 0.00168%, amr) (gnomAD).

What do computational predictors say about RIN2 p.Arg89Gly (c.265C>G)?

AlphaMissense predicts likely pathogenic (score 0.8679) — an in-silico prediction, not a clinical call.

RIN2 p.Arg89Gly

c.265C>G · rs1163956426 · VCV2062096

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8679 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00168%, amr)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.8679	likely pathogenic
REVEL	0.163	moderately benign-leaning
SaProt	LLR -10.11	damaging
⇒ AlphaMissense and SaProt call this damaging; REVEL does not.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 4.9	GERP -2.1, phastCons 1
Regional constraint	o/e 1.06	unconstrained · MANE · 86 kb · p 0.14 · regional, not allelic
Overall
CADD	23.6	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 0.00168% Admixed American · 1/59,640 alleles

Overall 0.000124% 2/1,610,654 alleles · very rare exomes 2/1,458,406 · genomes 0/152,248 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00168%	59,640
European (non-Finnish)	8.48e-05%	1,178,624

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.Arg89Gly
Coding: c.265C>G
MANE Select: NM_018993
dbSNP: rs1163956426
Type: single nucleotide variant
Location: chr20:19956721 (GRCh38)
Gene constraint: LOEUF 0.637 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 64.30

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

Similar variants

RIN2 p.Arg89Gln Uncertain significance ★★ ⚠ 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
RIN2 p.Arg290Leu 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-arg89gly (accessed [today's date]).

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