Is INTS9 p.Arg501Gln (c.1502G>A) pathogenic?

INTS9 p.Arg501Gln (c.1502G>A) is classified Uncertain significance in INTS9 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-06-07). AlphaMissense: ambiguous (0.4635); Very rare (popmax 0.00401%, afr).

How common is INTS9 p.Arg501Gln (c.1502G>A) in the general population?

INTS9 p.Arg501Gln (c.1502G>A) is very rare (popmax 0.00401%, afr) (gnomAD).

What do computational predictors say about INTS9 p.Arg501Gln (c.1502G>A)?

AlphaMissense predicts ambiguous (score 0.4635) — an in-silico prediction, not a clinical call.

INTS9 p.Arg501Gln

c.1502G>A · VCV4039087

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4635 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00401%, afr)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense indeterminate

Computational evidence

Protein change
AlphaMissense	0.4635	ambiguous
REVEL	0.133	moderately benign-leaning
SaProt	LLR -8.09	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense is indeterminate.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 7.5	GERP 1.8, phastCons 1
Regional constraint	o/e 0.93	unconstrained · MANE · 9,768 bp · p 0.25 · regional, not allelic
Overall
CADD	24.3	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 0.00401% African / African-American · 3/74,906 alleles

Filtering AF 0.00106% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000495%

Overall 0.000558% 9/1,613,954 alleles · very rare exomes 7/1,461,816 · genomes 2/152,138 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00401%	24,969
Remaining individualsnot grpmax-eligible	0.0016%	62,478
European (non-Finnish)	0.000424%	236,003

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: INTS9
Protein: p.Arg501Gln
Coding: c.1502G>A
MANE Select: NM_018250
Type: single nucleotide variant
Location: chr8:28775820 (GRCh38)
Gene constraint: LOEUF 0.871 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 90.95 · 15 PDB

Full INTS9 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

INTS9 p.Leu417Pro Uncertain significance ★★ ⚠ same type
INTS9 p.Ala208Val Uncertain significance ★ ⚠ same type
INTS9 p.Ala286Asp Uncertain significance ★ ⚠ same type
INTS9 p.Ala319Val Uncertain significance ★ ⚠ same type
INTS9 p.Ala506Thr Uncertain significance ★ ⚠ same type
INTS9 p.Ala560Thr Uncertain significance ★ ⚠ same type
INTS9 p.Arg401Cys Uncertain significance ★ ⚠ same type
INTS9 p.Arg401His 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/ints9-p-arg501gln (accessed [today's date]).

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