Is RIN2 p.Tyr834Phe (c.2501A>T) pathogenic?

RIN2 p.Tyr834Phe (c.2501A>T) is classified Conflicting classifications of pathogenicity in RIN2 (ClinVar, Conflicting submitters, 5 submitters; last evaluated 2026-08-06). AlphaMissense: likely benign (0.2435); Rare (popmax 0.271%, nfe).

How common is RIN2 p.Tyr834Phe (c.2501A>T) in the general population?

RIN2 p.Tyr834Phe (c.2501A>T) is rare (popmax 0.271%, nfe) (gnomAD).

What do computational predictors say about RIN2 p.Tyr834Phe (c.2501A>T)?

AlphaMissense predicts likely benign (score 0.2435) — an in-silico prediction, not a clinical call.

RIN2 p.Tyr834Phe

c.2501A>T · rs183141566 · VCV218547

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 5 submitters

AlphaMissense

likely benign

0.2435 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.271%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2435	likely benign
REVEL	0.168	moderately benign-leaning
SaProt	LLR -8.03	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.4	GERP 6.1, phastCons 1
Regional constraint	o/e 0.89	unconstrained · MANE · 4,195 bp · p 0.15 · regional, not allelic
Overall
CADD	24.4	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.271% European (non-Finnish) · 3,202/1,179,896 alleles

Filtering AF 0.264% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.26%

Overall 0.208% 3,350/1,614,008 alleles · rare exomes 3,193/1,461,704 · genomes 157/152,304 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.271%	368
Remaining individualsnot grpmax-eligible	0.115%	868
Admixed American	0.0583%	1,715
Middle Eastern	0.0495%	2,021
African / African-American	0.0267%	3,752
Finnishnot grpmax-eligible	0.025%	4,001
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,604
South Asian	0.0011%	91,082

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.Tyr834Phe
Coding: c.2501A>T
MANE Select: NM_018993
dbSNP: rs183141566
Type: single nucleotide variant
Location: chr20:20000749 (GRCh38)
Gene constraint: LOEUF 0.637 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 64.30
Residue 834: the ras-associating 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-tyr834phe (accessed [today's date]).

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