Is INTS1 p.Gly722= (c.2166G>A) pathogenic?

INTS1 p.Gly722= (c.2166G>A) is classified Likely benign in INTS1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-11-24). Ultra-rare (popmax 0.0193%, afr); Associated with Inborn genetic diseases.

What condition is associated with INTS1 p.Gly722= (c.2166G>A)?

INTS1 p.Gly722= (c.2166G>A) is associated with Inborn genetic diseases (ClinVar).

How common is INTS1 p.Gly722= (c.2166G>A) in the general population?

INTS1 p.Gly722= (c.2166G>A) is ultra-rare (popmax 0.0193%, afr) (gnomAD).

INTS1 p.Gly722=

c.2166G>A · VCV3529400

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0193%, afr)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>A here scores Δ0.20 · evaluated, not missing
Constraint at this position
Conservation	phyloP 1.3	GERP 0.15, phastCons 1
Overall
CADD	13.38	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0193% African / African-American · 14/72,648 alleles

Filtering AF 0.0116% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00931%

Overall 0.00117% 18/1,536,128 alleles · ultra-rare exomes 11/1,383,914 · genomes 7/152,214 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0193%	5,189
Remaining individualsnot grpmax-eligible	0.00506%	19,745
Admixed American	0.00206%	48,650

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.Gly722=
Coding: c.2166G>A
MANE Select: NM_001080453
Type: single nucleotide variant
Location: chr7:1489682 (GRCh38)
Gene constraint: LOEUF 0.785 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 75.49 · 8 PDB

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

INTS1 c.1283+5G>A Uncertain significance ★★ same condition
INTS1 c.2977-5C>T Uncertain significance ★★ same condition
INTS1 p.Ala1505Val Uncertain significance ★★ ⚠ same condition
INTS1 p.Ala1854Val Uncertain significance ★★ ⚠ same condition
INTS1 p.Ala2155Val Uncertain significance ★★ ⚠ same condition
INTS1 p.Ala2175Thr Uncertain significance ★★ ⚠ same condition
INTS1 p.Ala4Thr Uncertain significance ★★ ⚠ same condition
INTS1 p.Arg1096Cys 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-gly722 (accessed [today's date]).

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