INTS1 c.950+14T>C

Q: Is INTS1 c.950+14T>C pathogenic?

INTS1 c.950+14T>C is classified Benign in INTS1 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2024-11-27). Common (popmax 76.2%, afr) — too common for a highly-penetrant pathogenic allele; Associated with neurodevelopmental disorder with cataracts, poor growth, and dysmorphic facies.

Q: What condition is associated with INTS1 c.950+14T>C?

INTS1 c.950+14T>C is associated with neurodevelopmental disorder with cataracts, poor growth, and dysmorphic facies (ClinVar).

Q: How common is INTS1 c.950+14T>C in the general population?

INTS1 c.950+14T>C is common (popmax 76.2%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

rs750005 · VCV1185486

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Common

common (popmax 76.2%, afr) — too common for a highly-penetrant pathogenic allele

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.
Splicing
Splice region	donor +14	near-intronic (+14 nt from the splice site)
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -13	GERP -3
Overall
CADD	0.003	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 76.2% African / African-American · 57,048/74,912 alleles

Filtering AF 75.6% ClinGen BA1/BS1 input FAF95, joint · FAF99 75.4%

Overall 44.8% 719,316/1,607,270 alleles · common exomes 637,995/1,455,134 · genomes 81,321/152,136 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	76.2%	1
East Asian	72.6%	1
Amishnot grpmax-eligible	59.9%	2
South Asian	49.9%	2
Finnishnot grpmax-eligible	49%	2
Middle Eastern	48.9%	2
Remaining individualsnot grpmax-eligible	46.1%	2
European (non-Finnish)	41.3%	2
Admixed American	40.6%	2
Ashkenazi Jewishnot grpmax-eligible	40.5%	2

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
Coding: c.950+14T>C
MANE Select: NM_001080453
dbSNP: rs750005
Type: single nucleotide variant
Location: chr7:1499241 (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

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

Similar variants

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
INTS1 c.2977-5C>T Uncertain significance ★★ same condition
INTS1 p.Ala745Thr Uncertain significance ★★ ⚠ same condition
INTS1 p.Arg1130Cys Uncertain significance ★★ ⚠ same condition
INTS1 p.Arg1685Gln Uncertain significance ★★ ⚠ same condition
INTS1 p.Arg1800Gln 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-c-950-plus-14t-c (accessed [today's date]).

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