Is INTS1 p.Asp1182Asn (c.3544G>A) pathogenic?

INTS1 p.Asp1182Asn (c.3544G>A) is classified Uncertain significance in INTS1 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-10-13). AlphaMissense: likely benign (0.0899); Very rare (popmax 0.00668%, eas); Associated with Inborn genetic diseases.

What condition is associated with INTS1 p.Asp1182Asn (c.3544G>A)?

INTS1 p.Asp1182Asn (c.3544G>A) is associated with Inborn genetic diseases (ClinVar).

How common is INTS1 p.Asp1182Asn (c.3544G>A) in the general population?

INTS1 p.Asp1182Asn (c.3544G>A) is very rare (popmax 0.00668%, eas) (gnomAD).

What do computational predictors say about INTS1 p.Asp1182Asn (c.3544G>A)?

AlphaMissense predicts likely benign (score 0.0899) — an in-silico prediction, not a clinical call.

INTS1 p.Asp1182Asn

c.3544G>A · rs746174016 · VCV2255211

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0899 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00668%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0899	likely benign
REVEL	0.053	moderately benign-leaning
SaProt	LLR -7.55	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 5.8	GERP 1.2, phastCons 1
Regional constraint	o/e 0.96	unconstrained · MANE · 21 kb · p 0.12 · regional, not allelic
Overall
CADD	22.6	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 0.00668% East Asian · 3/44,888 alleles

Filtering AF 0.00177% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000891%

Overall 0.000744% 12/1,612,326 alleles · very rare exomes 9/1,460,082 · genomes 3/152,244 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00668%	14,963
African / African-American	0.00267%	37,474
South Asian	0.0022%	45,533
European (non-Finnish)	0.000424%	235,938

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.Asp1182Asn
Coding: c.3544G>A
MANE Select: NM_001080453
dbSNP: rs746174016
Type: single nucleotide variant
Location: chr7:1482705 (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

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

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INTS1 p.Ala2155Val Uncertain significance ★★ ⚠ same condition
INTS1 p.Ala2175Thr Uncertain significance ★★ ⚠ same condition
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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-asp1182asn (accessed [today's date]).

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