Is INTS1 p.Ile1884Met (c.5652C>G) pathogenic?

INTS1 p.Ile1884Met (c.5652C>G) is classified Uncertain significance in INTS1 (ClinVar, Single submitter, 1 submitter; last evaluated 2026-06-06). AlphaMissense: likely benign (0.0764); Rare (popmax 0.135%, mid).

How common is INTS1 p.Ile1884Met (c.5652C>G) in the general population?

INTS1 p.Ile1884Met (c.5652C>G) is rare (popmax 0.135%, mid) (gnomAD).

What do computational predictors say about INTS1 p.Ile1884Met (c.5652C>G)?

AlphaMissense predicts likely benign (score 0.0764) — an in-silico prediction, not a clinical call.

INTS1 p.Ile1884Met

c.5652C>G · rs768241069 · VCV2413062

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0764 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.135%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0764	likely benign
REVEL	0.17	moderately benign-leaning
SaProt	LLR -6.27	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -4.6	GERP -2.8
Regional constraint	o/e 1.09	unconstrained · MANE · 12 kb · p 0.001 · regional, not allelic
Overall
CADD	0.322	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.135% Middle Eastern · 7/5,196 alleles

Filtering AF 0.0632% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0448%

Overall 0.0015% 24/1,599,374 alleles · rare exomes 23/1,447,052 · genomes 1/152,322 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.135%	742
European (non-Finnish)	0.00136%	73,403
South Asian	0.00111%	90,428

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.Ile1884Met
Coding: c.5652C>G
MANE Select: NM_001080453
dbSNP: rs768241069
Type: single nucleotide variant
Location: chr7:1474345 (GRCh38)
Gene constraint: LOEUF 0.785 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 75.49 · 8 PDB
Residue 1884: an α-helix; a UniProt-annotated variant site (in ndcagf; decreased protein abundance)

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

Similar variants

INTS1 p.Ile1884= Likely benign ★ same residue
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

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-ile1884met (accessed [today's date]).

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