Is INTS2 c.432+5A>G pathogenic?

INTS2 c.432+5A>G is classified Likely benign in INTS2 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2023-06-05). Rare (popmax 0.615%, nfe); Associated with INTS2-related disorder.

What condition is associated with INTS2 c.432+5A>G?

INTS2 c.432+5A>G is associated with INTS2-related disorder (ClinVar).

How common is INTS2 c.432+5A>G in the general population?

INTS2 c.432+5A>G is rare (popmax 0.615%, nfe) (gnomAD).

INTS2 c.432+5A>G

rs61751979 · VCV3050653

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

rare (popmax 0.615%, nfe)

Conditions

INTS2-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
Splice region	donor +5	donor splice region (+5, within the first 6 intronic nt) · inside the BP7-excluded zone
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.083	GERP -4.6, phastCons 0.4
Non-coding constraint	Z 0.62	1 kb window · o/e 0.96 · regional · uncalibrated
Overall
CADD	14.07	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.615% European (non-Finnish) · 7,252/1,178,334 alleles

Filtering AF 0.604% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.599%

Overall 0.494% 7,955/1,610,680 alleles · rare exomes 7,470/1,458,370 · genomes 485/152,310 · joint denominator

Ancestry group	Frequency	1 in
Amishnot grpmax-eligible	2.19%	46
European (non-Finnish)grpmax	0.615%	162
Remaining individualsnot grpmax-eligible	0.484%	207
Finnishnot grpmax-eligible	0.332%	301
Admixed American	0.119%	838
African / African-American	0.101%	987
Middle Eastern	0.0495%	2,019
South Asian	0.0155%	6,452
Ashkenazi Jewishnot grpmax-eligible	0.0102%	9,809
East Asian	0.00446%	22,430

Amish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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: INTS2
Coding: c.432+5A>G
MANE Select: NM_001351695
dbSNP: rs61751979
Type: single nucleotide variant
Location: chr17:61924956 (GRCh38)
Gene constraint: LOEUF 0.491 · pLI 0.98 (gnomAD)
Structure: AlphaFold pLDDT 78.90 · 8 PDB

Full INTS2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

INTS2-related disorder

Similar variants

INTS2 p.Gln583= Benign same condition
INTS2 p.Val352Ala Likely benign same condition
INTS2 c.-17A>G Uncertain significance ★ ⚠ same type
INTS2 c.-1A>G Uncertain significance ★ ⚠ same type
INTS2 c.-3A>G Uncertain significance ★ ⚠ same type
INTS2 p.Ala1125Ser Uncertain significance ★ ⚠ same type
INTS2 p.Ala379Val Uncertain significance ★ same type
INTS2 p.Ala400Asp 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/ints2-c-432-plus-5a-g (accessed [today's date]).

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