Is RINT1 p.Pro247fs (c.740del) pathogenic?

RINT1 p.Pro247fs (c.740del) is classified Conflicting classifications of pathogenicity in RINT1 (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2024-01-19). Very rare (popmax 8.47e-05%, nfe).

How common is RINT1 p.Pro247fs (c.740del) in the general population?

RINT1 p.Pro247fs (c.740del) is very rare (popmax 8.47e-05%, nfe) (gnomAD).

RINT1 p.Pro247fs

c.740del · rs1352349454 · VCV963516

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

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

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 6 of 15
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 0.21	GERP -0.096, phastCons 0.002

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.47e-05% European (non-Finnish) · 1/1,180,000 alleles

Overall 6.2e-05% 1/1,614,012 alleles · very rare exomes 1/1,461,882 · genomes 0/152,130 · 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.Pro247fs
Coding: c.740del
MANE Select: NM_021930
dbSNP: rs1352349454
Type: Deletion
Location: chr7:105547230 (GRCh38)
Gene constraint: LOEUF 0.931 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 85.97
Residue 247: the rint1/tip20 domain

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

Similar variants

RINT1 p.Pro247Leu Uncertain significance ★ ⚠ same residue
RINT1 p.Pro247= Likely benign ★ same residue
RINT1 p.Asn328del Uncertain significance ★★ same type
RINT1 p.Asp605del Uncertain significance ★★ same type
RINT1 c.515+2_515+9del Likely pathogenic ★ same type
RINT1 p.Ala215fs Pathogenic ★ same type
RINT1 p.Asn109fs Pathogenic ★ same type
RINT1 p.Asp403fs Likely pathogenic ★ 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-pro247fs (accessed [today's date]).

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