Is RIN2 p.Arg83Gly (c.247A>G) pathogenic?

RIN2 p.Arg83Gly (c.247A>G) is classified Uncertain significance in RIN2 (ClinVar, Multiple submitters, 5 submitters; last evaluated 2025-01-19). AlphaMissense: likely benign (0.1602); Ultra-rare (popmax 0.0304%, nfe); Associated with Inborn genetic diseases.

What condition is associated with RIN2 p.Arg83Gly (c.247A>G)?

RIN2 p.Arg83Gly (c.247A>G) is associated with Inborn genetic diseases (ClinVar).

How common is RIN2 p.Arg83Gly (c.247A>G) in the general population?

RIN2 p.Arg83Gly (c.247A>G) is ultra-rare (popmax 0.0304%, nfe) (gnomAD).

What do computational predictors say about RIN2 p.Arg83Gly (c.247A>G)?

AlphaMissense predicts likely benign (score 0.1602) — an in-silico prediction, not a clinical call.

RIN2 p.Arg83Gly

c.247A>G · rs375970512 · VCV425265

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

AlphaMissense

likely benign

0.1602 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0304%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1602	likely benign
REVEL	0.18	moderately benign-leaning
SaProt	LLR -5.41	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6	GERP -3.3, phastCons 1
Regional constraint	o/e 1.06	unconstrained · MANE · 86 kb · p 0.14 · regional, not allelic
Overall
CADD	21.8	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0304% European (non-Finnish) · 358/1,179,356 alleles

Filtering AF 0.0277% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0267%

Overall 0.023% 371/1,612,436 alleles · ultra-rare exomes 352/1,460,256 · genomes 19/152,180 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0304%	3,294
Remaining individualsnot grpmax-eligible	0.0112%	8,919
Admixed American	0.00669%	14,954
African / African-American	0.00267%	37,450

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.Arg83Gly
Coding: c.247A>G
MANE Select: NM_018993
dbSNP: rs375970512
Type: single nucleotide variant
Location: chr20:19956703 (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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

RIN2 p.Arg83Ser Uncertain significance ★ ⚠ same residue
RIN2 p.Ala205Val Uncertain significance ★★ ⚠ same condition
RIN2 p.Ala72Thr Uncertain significance ★★ ⚠ same condition
RIN2 p.Arg135Cys Uncertain significance ★★ ⚠ same condition
RIN2 p.Arg170Trp Uncertain significance ★★ ⚠ same condition
RIN2 p.Arg255Thr Uncertain significance ★★ ⚠ same condition
RIN2 p.Arg290Leu Uncertain significance ★★ ⚠ same condition
RIN2 p.Arg303Gln Uncertain significance ★★ ⚠ 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-arg83gly (accessed [today's date]).

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