Is INTS1 p.Arg1800fs (c.5398dup) pathogenic?

INTS1 p.Arg1800fs (c.5398dup) is classified Pathogenic in INTS1 (ClinVar, No assertion criteria, 2 submitters; last evaluated 2020-10-19). Very rare (popmax 0.00196%, amr); Associated with neurodevelopmental disorder with cataracts, poor growth, and dysmorphic facies.

What condition is associated with INTS1 p.Arg1800fs (c.5398dup)?

INTS1 p.Arg1800fs (c.5398dup) is associated with neurodevelopmental disorder with cataracts, poor growth, and dysmorphic facies (ClinVar).

How common is INTS1 p.Arg1800fs (c.5398dup) in the general population?

INTS1 p.Arg1800fs (c.5398dup) is very rare (popmax 0.00196%, amr) (gnomAD).

INTS1 p.Arg1800fs

c.5398dup · rs1562487424 · VCV689522

Pathogenic No assertion criteria

Classification

Pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 2 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00196%, amr)

Conditions

neurodevelopmental disorder with cataracts, poor growth, and dysmorphic facies

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 39 of 48
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -0.26	GERP -2.6

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00196% Admixed American · 1/50,988 alleles

Overall 6.47e-05% 1/1,544,734 alleles · very rare exomes 1/1,392,364 · genomes 0/152,370 · 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: INTS1
Protein: p.Arg1800fs
Coding: c.5398dup
MANE Select: NM_001080453
dbSNP: rs1562487424
Type: Duplication
Location: chr7:1476051 (GRCh38)
Gene constraint: LOEUF 0.785 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 75.49 · 8 PDB
Residue 1800: an α-helix; a UniProt-annotated variant site (in ndcagf; decreased protein abundance)

Full INTS1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

neurodevelopmental disorder with cataracts, poor growth, and dysmorphic facies — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

INTS1 p.Arg1800Gln Uncertain significance ★★ ⚠ same residue
INTS1 p.Val180fs Likely pathogenic ★ same condition
INTS1 p.Phe2104fs Uncertain significance ★ same condition
INTS1 p.Thr1045fs Uncertain significance ★ same condition
INTS1 c.3424_3429+20del Likely pathogenic ★★ same condition
INTS1 c.3430-2A>C Likely pathogenic ★★ same condition
INTS1 p.Arg101Ter Likely pathogenic ★★ same condition
INTS1 c.1283+5G>A Uncertain significance ★★ same condition

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/ints1-p-arg1800fs (accessed [today's date]).

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