Is INTS1 p.Arg1427Cys (c.4279C>T) pathogenic?

INTS1 p.Arg1427Cys (c.4279C>T) is classified Conflicting classifications of pathogenicity in INTS1 (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2024-11-19). AlphaMissense: likely benign (0.1119); Rare (popmax 0.16%, afr); Associated with Inborn genetic diseases.

What condition is associated with INTS1 p.Arg1427Cys (c.4279C>T)?

INTS1 p.Arg1427Cys (c.4279C>T) is associated with Inborn genetic diseases (ClinVar).

How common is INTS1 p.Arg1427Cys (c.4279C>T) in the general population?

INTS1 p.Arg1427Cys (c.4279C>T) is rare (popmax 0.16%, afr) (gnomAD).

What do computational predictors say about INTS1 p.Arg1427Cys (c.4279C>T)?

AlphaMissense predicts likely benign (score 0.1119) — an in-silico prediction, not a clinical call.

INTS1 p.Arg1427Cys

c.4279C>T · rs202052814 · VCV1801175

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1119 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.16%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1119	likely benign
REVEL	0.192	benign-leaning
SaProt	LLR -9.64	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 8.5	GERP 1.4, phastCons 1
Regional constraint	o/e 1.09	unconstrained · MANE · 12 kb · p 0.001 · regional, not allelic
Overall
CADD	27.1	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 0.16% African / African-American · 119/74,270 alleles

Filtering AF 0.137% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.128%

Overall 0.0116% 183/1,577,812 alleles · rare exomes 86/1,425,412 · genomes 97/152,400 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.16%	624
Ashkenazi Jewishnot grpmax-eligible	0.0518%	1,929
Admixed American	0.0361%	2,773
Remaining individualsnot grpmax-eligible	0.0213%	4,704
South Asian	0.0128%	7,805
European (non-Finnish)	0.00043%	232,608

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.Arg1427Cys
Coding: c.4279C>T
MANE Select: NM_001080453
dbSNP: rs202052814
Type: single nucleotide variant
Location: chr7:1479480 (GRCh38)
Gene constraint: LOEUF 0.785 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 75.49 · 8 PDB
Residue 1427: an α-helix

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

INTS1 p.Arg1427His Conflicting classifications of pathogenicity ★ ⚠ same residue
INTS1 c.1283+5G>A Uncertain significance ★★ same condition
INTS1 c.2977-5C>T Uncertain significance ★★ same condition
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

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-arg1427cys (accessed [today's date]).

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