Is RIN2 p.Ala315= (c.945T>G) pathogenic?

RIN2 p.Ala315= (c.945T>G) is classified Likely benign in RIN2 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2023-02-21). Very rare (popmax 0.000235%, nfe); Associated with RIN2-related disorder.

What condition is associated with RIN2 p.Ala315= (c.945T>G)?

RIN2 p.Ala315= (c.945T>G) is associated with RIN2-related disorder (ClinVar).

How common is RIN2 p.Ala315= (c.945T>G) in the general population?

RIN2 p.Ala315= (c.945T>G) is very rare (popmax 0.000235%, nfe) (gnomAD).

RIN2 p.Ala315=

c.945T>G · rs1475873736 · VCV3045478

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.000235%, nfe)

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 2.7	GERP -0.014, phastCons 1
Overall
CADD	10.15	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000235% European (non-Finnish) · 2/851,548 alleles

Filtering AF 3.9e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.5e-05%

Overall 0.000172% 2/1,163,858 alleles · very rare exomes 2/1,048,070 · genomes 0/115,788 · 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.Ala315=
Coding: c.945T>G
MANE Select: NM_018993
dbSNP: rs1475873736
Type: single nucleotide variant
Location: chr20:19974970 (GRCh38)
Gene constraint: LOEUF 0.637 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 64.30
Residue 315: the 'disordered' region

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

Disease context

RIN2-related disorder

Similar variants

RIN2 p.Ala315Ser Uncertain significance ★ ⚠ same residue
RIN2 p.Ala315Pro Likely benign same residue
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.Arg632= Likely benign same condition
RIN2 p.His250= Likely benign 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-ala315 (accessed [today's date]).

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