Is RIN2 p.His250= (c.750T>C) pathogenic?

RIN2 p.His250= (c.750T>C) is classified Likely benign in RIN2 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2022-11-23). Absent from gnomAD v4.1; Associated with RIN2-related disorder.

What condition is associated with RIN2 p.His250= (c.750T>C)?

RIN2 p.His250= (c.750T>C) is associated with RIN2-related disorder (ClinVar).

How common is RIN2 p.His250= (c.750T>C) in the general population?

RIN2 p.His250= (c.750T>C) is absent from gnomAD v4.1 (gnomAD).

RIN2 p.His250=

c.750T>C · rs2515505684 · VCV3051550

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

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 2.3	GERP 1.2, phastCons 1
Overall
CADD	7.98	PHRED · no single calibrated threshold — expert panels disagree

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.His250=
Coding: c.750T>C
MANE Select: NM_018993
dbSNP: rs2515505684
Type: single nucleotide variant
Location: chr20:19974775 (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

RIN2-related disorder

Similar variants

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.Arg632= Likely benign same condition
RIN2 p.Pro313= Likely benign same condition
RIN2 p.Ala205Val 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-his250 (accessed [today's date]).

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