Is RINT1 p.Thr484= (c.1452T>A) pathogenic?

RINT1 p.Thr484= (c.1452T>A) is classified Likely benign in RINT1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2022-09-07). Ultra-rare (popmax 0.0102%, amr).

How common is RINT1 p.Thr484= (c.1452T>A) in the general population?

RINT1 p.Thr484= (c.1452T>A) is ultra-rare (popmax 0.0102%, amr) (gnomAD).

RINT1 p.Thr484=

c.1452T>A · rs770775698 · VCV697949

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0102%, amr)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -0.78	GERP -0.64, phastCons 0.001
Overall
CADD	4.961	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0102% Admixed American · 6/58,752 alleles

Filtering AF 0.00436% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.003%

Overall 0.000622% 10/1,607,692 alleles · ultra-rare exomes 8/1,455,474 · genomes 2/152,218 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0102%	9,792
African / African-American	0.00536%	18,662

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.Thr484=
Coding: c.1452T>A
MANE Select: NM_021930
dbSNP: rs770775698
Type: single nucleotide variant
Location: chr7:105551688 (GRCh38)
Gene constraint: LOEUF 0.931 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 85.97
Residue 484: the rint1/tip20 domain

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

Similar variants

RINT1 p.Thr484Ile Uncertain significance ★★ ⚠ same residue
RINT1 p.Thr484Ser Uncertain significance ★ ⚠ 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
RINT1 p.Ala138Thr 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-thr484 (accessed [today's date]).

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