Is RIN2 p.Glu417Asp (c.1251A>C) pathogenic?

RIN2 p.Glu417Asp (c.1251A>C) is classified Uncertain significance in RIN2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-08-24). AlphaMissense: likely benign (0.0687); Absent from gnomAD v4.1.

How common is RIN2 p.Glu417Asp (c.1251A>C) in the general population?

RIN2 p.Glu417Asp (c.1251A>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about RIN2 p.Glu417Asp (c.1251A>C)?

AlphaMissense predicts likely benign (score 0.0687) — an in-silico prediction, not a clinical call.

RIN2 p.Glu417Asp

c.1251A>C · rs939386125 · VCV2113824

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0687 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0687	likely benign
REVEL	0.062	moderately benign-leaning
SaProt	LLR -6.14	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 1.2	GERP -0.79, phastCons 1
Regional constraint	o/e 1.06	unconstrained · MANE · 86 kb · p 0.14 · regional, not allelic
Overall
CADD	14.45	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: RIN2
Protein: p.Glu417Asp
Coding: c.1251A>C
MANE Select: NM_018993
dbSNP: rs939386125
Type: single nucleotide variant
Location: chr20:19975276 (GRCh38)
Gene constraint: LOEUF 0.637 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 64.30
Residue 417: the 'disordered' region

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

Similar variants

RIN2 p.Glu417= 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
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-glu417asp (accessed [today's date]).

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