Is RINT1 p.Arg710Trp (c.2128C>T) pathogenic?

RINT1 p.Arg710Trp (c.2128C>T) is classified Uncertain significance in RINT1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-04-17). AlphaMissense: likely pathogenic (0.6413); Very rare (popmax 0.00667%, amr).

How common is RINT1 p.Arg710Trp (c.2128C>T) in the general population?

RINT1 p.Arg710Trp (c.2128C>T) is very rare (popmax 0.00667%, amr) (gnomAD).

What do computational predictors say about RINT1 p.Arg710Trp (c.2128C>T)?

AlphaMissense predicts likely pathogenic (score 0.6413) — an in-silico prediction, not a clinical call.

RINT1 p.Arg710Trp

c.2128C>T · rs777291719 · VCV856347

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.6413 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00667%, amr)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

⚠ Built without this gene's context — gene constraint and dosage, protein structure, pathways, panels and related-variant links were not looked up for this page. why

Computational evidence

Protein change
AlphaMissense	0.6413	likely pathogenic
REVEL	0.637	indeterminate
SaProt	LLR -12.82	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL is indeterminate.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 1.1	GERP 3.3, phastCons 0.51
Regional constraint	o/e 0.96	unconstrained · MANE · 35 kb · p 0.28 · regional, not allelic
Overall
CADD	29.0	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00667% Admixed American · 4/59,960 alleles

Filtering AF 0.00226% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00135%

Overall 0.000496% 8/1,613,762 alleles · very rare exomes 7/1,461,566 · genomes 1/152,196 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00667%	14,990
South Asian	0.0011%	91,068
European (non-Finnish)	0.000254%	393,298

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.Arg710Trp
Coding: c.2128C>T
MANE Select: NM_021930
dbSNP: rs777291719
Type: single nucleotide variant
Location: chr7:105565590 (GRCh38)

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

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-arg710trp (accessed [today's date]).

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