Is RINT1 p.Ile244= (c.732C>T) pathogenic?

RINT1 p.Ile244= (c.732C>T) is classified Benign/Likely benign in RINT1 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2026-01-04). Low-frequency (popmax 2.08%, afr).

How common is RINT1 p.Ile244= (c.732C>T) in the general population?

RINT1 p.Ile244= (c.732C>T) is low-frequency (popmax 2.08%, afr) (gnomAD).

RINT1 p.Ile244=

c.732C>T · rs148050825 · VCV241414

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

low-frequency (popmax 2.08%, afr)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Splicing
SpliceAI	Δ0.20	acceptor loss, 42 bp away · masked 0 · deltas
Pangolin	Δ0.26	loss · gain 0.00 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP -2.1	GERP -4.3
Overall
CADD	2.917	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 2.08% African / African-American · 1,561/75,028 alleles

Filtering AF 1.99% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.96%

Overall 0.107% 1,732/1,614,158 alleles · low-frequency exomes 885/1,461,886 · genomes 847/152,272 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	2.08%	48
Remaining individualsnot grpmax-eligible	0.115%	868
Admixed American	0.09%	1,111
Middle Eastern	0.0825%	1,212
South Asian	0.00329%	30,362
European (non-Finnish)	0.00314%	31,893

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.Ile244=
Coding: c.732C>T
MANE Select: NM_021930
dbSNP: rs148050825
Type: single nucleotide variant
Location: chr7:105547226 (GRCh38)
Gene constraint: LOEUF 0.931 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 85.97
Residue 244: the rint1/tip20 domain

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

Similar variants

RINT1 p.Ile244Phe Uncertain significance ★ ⚠ same residue
RINT1 p.Ile244Val 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-ile244 (accessed [today's date]).

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