Is RIN2 p.Arg310fs (c.928_929del) pathogenic?

RIN2 p.Arg310fs (c.928929del) is classified Uncertain significance in RIN2 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2018-09-16). Rare (popmax 0.646%, nfe).

How common is RIN2 p.Arg310fs (c.928_929del) in the general population?

RIN2 p.Arg310fs (c.928_929del) is rare (popmax 0.646%, nfe) (gnomAD).

RIN2 p.Arg310fs

c.928_929del · rs1568687231 · VCV591322

Uncertain significance No assertion criteria

Classification

Uncertain significance

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

rare (popmax 0.646%, nfe)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 9 of 13
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 3.2	GERP 2.2, phastCons 1
Overall
CADD	34.0	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.646% European (non-Finnish) · 7,096/1,099,118 alleles

Filtering AF 0.633% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.628%

Overall 0.511% 7,793/1,524,244 alleles · rare exomes 7,786/1,373,450 · genomes 7/150,794 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.646%	155
Remaining individualsnot grpmax-eligible	0.454%	220
South Asian	0.199%	502
African / African-American	0.193%	517
Middle Eastern	0.17%	587
Ashkenazi Jewishnot grpmax-eligible	0.159%	631
East Asian	0.088%	1,136
Admixed American	0.0151%	6,633
Finnishnot grpmax-eligible	0.00473%	21,128

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.Arg310fs
Coding: c.928_929del
MANE Select: NM_018993
dbSNP: rs1568687231
Type: Deletion
Location: chr20:19974953 (GRCh38)
Gene constraint: LOEUF 0.637 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 64.30
Residue 310: the 'disordered' region

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

Similar variants

RIN2 p.Arg310= Likely benign ★★ same residue
RIN2 p.Arg310Met Uncertain significance ★ ⚠ same residue
RIN2 p.Asn799fs Uncertain significance ★★ same type
RIN2 c.-36-2865del Benign ★★ same type
RIN2 p.Asn44fs Pathogenic ★ same type
RIN2 p.Ile272fs Pathogenic ★ same type
RIN2 p.Ile578fs Pathogenic ★ same type
RIN2 p.Ser16fs Pathogenic ★ 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-arg310fs (accessed [today's date]).

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