INTS1 p.Ala63=

Q: Is INTS1 p.Ala63= (c.189C>T) pathogenic?

INTS1 p.Ala63= (c.189C>T) is classified Benign in INTS1 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2024-11-27). Common (popmax 72.5%, eas) — 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 p.Ala63= (c.189C>T)?

INTS1 p.Ala63= (c.189C>T) is associated with neurodevelopmental disorder with cataracts, poor growth, and dysmorphic facies (ClinVar).

Q: How common is INTS1 p.Ala63= (c.189C>T) in the general population?

INTS1 p.Ala63= (c.189C>T) is common (popmax 72.5%, eas) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.189C>T · rs3752714 · VCV1185489

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Common

common (popmax 72.5%, eas) — 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
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -6.2	GERP -4.4
Overall
CADD	0.34	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 72.5% East Asian · 32,520/44,832 alleles

Filtering AF 71.9% ClinGen BA1/BS1 input FAF95, joint · FAF99 71.6%

Overall 44.3% 714,026/1,612,572 alleles · common exomes 635,068/1,460,542 · genomes 78,958/152,030 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	72.5%	1
African / African-American	71.2%	1
Amishnot grpmax-eligible	60%	2
Finnishnot grpmax-eligible	49%	2
Middle Eastern	48%	2
South Asian	47.3%	2
Remaining individualsnot grpmax-eligible	45.3%	2
European (non-Finnish)	41.2%	2
Ashkenazi Jewishnot grpmax-eligible	40.4%	2
Admixed American	40.2%	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
Protein: p.Ala63=
Coding: c.189C>T
MANE Select: NM_001080453
dbSNP: rs3752714
Type: single nucleotide variant
Location: chr7:1503061 (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-p-ala63 (accessed [today's date]).

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