Is INTS1 p.Lys370Arg (c.1109A>G) pathogenic?

INTS1 p.Lys370Arg (c.1109A>G) is classified Benign in INTS1 (ClinVar, Single submitter, 1 submitter; last evaluated 2019-12-31). AlphaMissense: likely benign (0.058); Low-frequency (popmax 1.91%, afr).

How common is INTS1 p.Lys370Arg (c.1109A>G) in the general population?

INTS1 p.Lys370Arg (c.1109A>G) is low-frequency (popmax 1.91%, afr) (gnomAD).

What do computational predictors say about INTS1 p.Lys370Arg (c.1109A>G)?

AlphaMissense predicts likely benign (score 0.058) — an in-silico prediction, not a clinical call.

INTS1 p.Lys370Arg

c.1109A>G · rs200286642 · VCV776190

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.058 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 1.91%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.058	likely benign
REVEL	0.081	moderately benign-leaning
SaProt	LLR -5.88	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 1.3	GERP 0.68, phastCons 0.87
Regional constraint	o/e 0.96	unconstrained · MANE · 21 kb · p 0.12 · regional, not allelic
Overall
CADD	14.93	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 1.91% African / African-American · 1,220/63,720 alleles

Filtering AF 1.83% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.79%

Overall 0.102% 1,401/1,378,194 alleles · low-frequency exomes 739/1,249,028 · genomes 662/129,166 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	1.91%	52
Admixed American	0.182%	551
Remaining individualsnot grpmax-eligible	0.157%	638
Middle Eastern	0.0565%	1,770
European (non-Finnish)	0.0023%	43,454
South Asian	0.00122%	81,884

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.Lys370Arg
Coding: c.1109A>G
MANE Select: NM_001080453
dbSNP: rs200286642
Type: single nucleotide variant
Location: chr7:1499003 (GRCh38)
Gene constraint: LOEUF 0.785 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 75.49 · 8 PDB
Residue 370: a turn

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-lys370arg (accessed [today's date]).

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