Is RIN2 p.Tyr720= (c.2160C>T) pathogenic?

RIN2 p.Tyr720= (c.2160C>T) is classified Likely benign in RIN2 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-09-06). Very rare (popmax 0.00451%, eas).

How common is RIN2 p.Tyr720= (c.2160C>T) in the general population?

RIN2 p.Tyr720= (c.2160C>T) is very rare (popmax 0.00451%, eas) (gnomAD).

RIN2 p.Tyr720=

c.2160C>T · rs1253230969 · VCV2079672

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00451%, eas)

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 1.5	GERP 6.5, phastCons 1
Overall
CADD	6.428	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00451% East Asian · 2/44,306 alleles

Filtering AF 0.000748% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00028%

Overall 0.000252% 4/1,590,246 alleles · very rare exomes 3/1,438,030 · genomes 1/152,216 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00451%	22,153
Remaining individualsnot grpmax-eligible	0.00162%	61,762
African / African-American	0.00134%	74,686

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.Tyr720=
Coding: c.2160C>T
MANE Select: NM_018993
dbSNP: rs1253230969
Type: single nucleotide variant
Location: chr20:19992259 (GRCh38)
Gene constraint: LOEUF 0.637 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 64.30
Residue 720: the vps9 domain

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

Similar variants

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
RIN2 p.Arg303Gln 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-tyr720 (accessed [today's date]).

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