Is RIN2 p.Glu417= (c.1251A>G) pathogenic?

RIN2 p.Glu417= (c.1251A>G) is classified Likely benign in RIN2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-11-19). Ultra-rare (popmax 0.0147%, afr).

How common is RIN2 p.Glu417= (c.1251A>G) in the general population?

RIN2 p.Glu417= (c.1251A>G) is ultra-rare (popmax 0.0147%, afr) (gnomAD).

RIN2 p.Glu417=

c.1251A>G · VCV3719363

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0147%, afr)

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 1.2	GERP -0.79, phastCons 1
Overall
CADD	6.839	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0147% African / African-American · 11/74,612 alleles

Filtering AF 0.00819% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00636%

Overall 0.00069% 11/1,595,348 alleles · ultra-rare exomes 5/1,443,134 · genomes 6/152,214 · 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.Glu417=
Coding: c.1251A>G
MANE Select: NM_018993
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.Glu417Asp 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-glu417 (accessed [today's date]).

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