Is INTS1 p.Ala1234= (c.3702C>T) pathogenic?

INTS1 p.Ala1234= (c.3702C>T) is classified Likely benign in INTS1 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-03-18). Ultra-rare (popmax 0.02%, afr); Associated with INTS1-related disorder.

What condition is associated with INTS1 p.Ala1234= (c.3702C>T)?

INTS1 p.Ala1234= (c.3702C>T) is associated with INTS1-related disorder (ClinVar).

How common is INTS1 p.Ala1234= (c.3702C>T) in the general population?

INTS1 p.Ala1234= (c.3702C>T) is ultra-rare (popmax 0.02%, afr) (gnomAD).

INTS1 p.Ala1234=

c.3702C>T · rs201306145 · VCV3047621

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.02%, afr)

Conditions

INTS1-related disorder

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 · G>T here scores Δ0.38 · evaluated, not missing
Constraint at this position
Conservation	phyloP -12	GERP -2.3
Overall
CADD	0.01	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.02% African / African-American · 15/74,916 alleles

Filtering AF 0.0123% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00989%

Overall 0.00237% 38/1,606,666 alleles · ultra-rare exomes 27/1,454,294 · genomes 11/152,372 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.02%	4,994
Admixed American	0.00503%	19,883
Remaining individualsnot grpmax-eligible	0.00161%	62,138
European (non-Finnish)	0.00153%	65,310
South Asian	0.0011%	90,672

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.Ala1234=
Coding: c.3702C>T
MANE Select: NM_001080453
dbSNP: rs201306145
Type: single nucleotide variant
Location: chr7:1482547 (GRCh38)
Gene constraint: LOEUF 0.785 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 75.49 · 8 PDB
Residue 1234: an α-helix

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

Disease context

INTS1-related disorder

Similar variants

INTS1 p.Ala1234Thr Uncertain significance ★ ⚠ same residue
INTS1 c.3156+8C>T Conflicting classifications of pathogenicity ★ same condition
INTS1 c.3850+76G>A Uncertain significance ★ same condition
INTS1 p.Gly73Ser Uncertain significance ⚠ same condition
INTS1 p.Lys435Asn Uncertain significance ⚠ same condition
INTS1 p.Met888Val Uncertain significance ⚠ same condition
INTS1 c.1138-4G>A Likely benign same condition
INTS1 c.2646+10G>A Likely benign 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-ala1234 (accessed [today's date]).

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