Is INTS1 p.Arg1810Trp (c.5428C>T) pathogenic?

INTS1 p.Arg1810Trp (c.5428C>T) is classified Uncertain significance in INTS1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-05-01). AlphaMissense: likely benign (0.085); Very rare (popmax 0.00489%, eas); Associated with Inborn genetic diseases.

What condition is associated with INTS1 p.Arg1810Trp (c.5428C>T)?

INTS1 p.Arg1810Trp (c.5428C>T) is associated with Inborn genetic diseases (ClinVar).

How common is INTS1 p.Arg1810Trp (c.5428C>T) in the general population?

INTS1 p.Arg1810Trp (c.5428C>T) is very rare (popmax 0.00489%, eas) (gnomAD).

What do computational predictors say about INTS1 p.Arg1810Trp (c.5428C>T)?

AlphaMissense predicts likely benign (score 0.085) — an in-silico prediction, not a clinical call.

INTS1 p.Arg1810Trp

c.5428C>T · VCV4038969

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.085 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00489%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.085	likely benign
REVEL	0.053	moderately benign-leaning
SaProt	LLR -8.93	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>C here scores Δ0.22 · evaluated, not missing
Constraint at this position
Conservation	phyloP 4.8	GERP 0.077, phastCons 1
Regional constraint	o/e 1.09	unconstrained · MANE · 12 kb · p 0.001 · regional, not allelic
Overall
CADD	21.6	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 0.00489% East Asian · 2/40,912 alleles

Filtering AF 0.00081% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000554%

Overall 0.00129% 20/1,545,708 alleles · very rare exomes 18/1,393,510 · genomes 2/152,198 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00489%	20,456
Finnishnot grpmax-eligible	0.00182%	55,046
Remaining individualsnot grpmax-eligible	0.00167%	59,968
African / African-American	0.00137%	73,018
European (non-Finnish)	0.00122%	81,905
South Asian	0.00119%	84,026

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.Arg1810Trp
Coding: c.5428C>T
MANE Select: NM_001080453
Type: single nucleotide variant
Location: chr7:1476022 (GRCh38)
Gene constraint: LOEUF 0.785 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 75.49 · 8 PDB
Residue 1810: a UniProt-annotated variant site (in ndcagf; decreased protein abundance)

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.Ala1505Val Uncertain significance ★★ ⚠ same condition
INTS1 p.Ala1854Val Uncertain significance ★★ ⚠ same condition
INTS1 p.Ala2155Val Uncertain significance ★★ ⚠ same condition
INTS1 p.Ala2175Thr Uncertain significance ★★ ⚠ same condition
INTS1 p.Ala4Thr Uncertain significance ★★ ⚠ same condition
INTS1 p.Arg1096Cys 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-arg1810trp (accessed [today's date]).

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