Is RINT1 p.Arg535Pro (c.1604G>C) pathogenic?

RINT1 p.Arg535Pro (c.1604G>C) is classified Uncertain significance in RINT1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-11-17). AlphaMissense: ambiguous (0.405); Very rare (popmax 8.47e-05%, nfe).

How common is RINT1 p.Arg535Pro (c.1604G>C) in the general population?

RINT1 p.Arg535Pro (c.1604G>C) is very rare (popmax 8.47e-05%, nfe) (gnomAD).

What do computational predictors say about RINT1 p.Arg535Pro (c.1604G>C)?

AlphaMissense predicts ambiguous (score 0.405) — an in-silico prediction, not a clinical call.

RINT1 p.Arg535Pro

c.1604G>C · VCV3433653

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.405 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.47e-05%, nfe)

Computational evidence

Protein change
AlphaMissense	0.405	ambiguous
REVEL	0.497	indeterminate
SaProt	LLR -10.72	damaging
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 3.6, phastCons 1
Regional constraint	o/e 0.96	unconstrained · MANE · 35 kb · p 0.28 · regional, not allelic
Overall
CADD	32.0	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 8.47e-05% European (non-Finnish) · 1/1,179,994 alleles

Overall 6.2e-05% 1/1,614,042 alleles · very rare exomes 1/1,461,772 · genomes 0/152,270 · 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: RINT1
Protein: p.Arg535Pro
Coding: c.1604G>C
MANE Select: NM_021930
Type: single nucleotide variant
Location: chr7:105555160 (GRCh38)
Gene constraint: LOEUF 0.931 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 85.97
Residue 535: the rint1/tip20 domain

Full RINT1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

RINT1 p.Arg535Gln Uncertain significance ★★ ⚠ same residue
RINT1 p.Arg535= Likely benign ★★ same residue
RINT1 p.Arg535Ter Conflicting classifications of pathogenicity ★ same residue
RINT1 c.1107+1G>T Likely pathogenic ★★ same type
RINT1 c.1886+5G>A Uncertain significance ★★ same type
RINT1 c.516-3C>T Uncertain significance ★★ same type
RINT1 c.840-12T>A Uncertain significance ★★ same type
RINT1 c.840-3C>G 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/rint1-p-arg535pro (accessed [today's date]).

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