Is INTS1 p.Arg382Gln (c.1145G>A) pathogenic?

INTS1 p.Arg382Gln (c.1145G>A) is classified Uncertain significance in INTS1 (ClinVar, Single submitter, 1 submitter; last evaluated 2020-11-01). AlphaMissense: likely pathogenic (0.7697); Very rare (popmax 0.00113%, sas).

How common is INTS1 p.Arg382Gln (c.1145G>A) in the general population?

INTS1 p.Arg382Gln (c.1145G>A) is very rare (popmax 0.00113%, sas) (gnomAD).

What do computational predictors say about INTS1 p.Arg382Gln (c.1145G>A)?

AlphaMissense predicts likely pathogenic (score 0.7697) — an in-silico prediction, not a clinical call.

INTS1 p.Arg382Gln

c.1145G>A · rs1782994531 · VCV1013532

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7697 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00113%, sas)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.7697	likely pathogenic
REVEL	0.159	moderately benign-leaning
SaProt	LLR -2.39	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.5	GERP 1.6, phastCons 1
Regional constraint	o/e 0.96	unconstrained · MANE · 21 kb · p 0.12 · regional, not allelic
Overall
CADD	30.0	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00113% South Asian · 1/88,668 alleles

Overall 0.000125% 2/1,603,346 alleles · very rare exomes 2/1,451,166 · genomes 0/152,180 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00113%	88,668
European (non-Finnish)	8.51e-05%	1,175,744

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.Arg382Gln
Coding: c.1145G>A
MANE Select: NM_001080453
dbSNP: rs1782994531
Type: single nucleotide variant
Location: chr7:1498845 (GRCh38)
Gene constraint: LOEUF 0.785 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 75.49 · 8 PDB
Residue 382: an α-helix

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

Similar variants

INTS1 c.3430-2A>C Likely pathogenic ★★ same type
INTS1 p.Arg101Ter Likely pathogenic ★★ same type
INTS1 p.Glu182Ter Likely pathogenic ★★ same type
INTS1 c.1283+5G>A Uncertain significance ★★ same type
INTS1 c.2977-5C>T Uncertain significance ★★ same type
INTS1 p.Ala1112Val Uncertain significance ★★ ⚠ same type
INTS1 p.Ala1505Val Uncertain significance ★★ ⚠ same type
INTS1 p.Ala1854Val 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/ints1-p-arg382gln (accessed [today's date]).

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