Is ARNT p.Arg472Gln (c.1415G>A) pathogenic?

ARNT p.Arg472Gln (c.1415G>A) is classified Uncertain significance in ARNT (ClinVar, Single submitter, 1 submitter; last evaluated 2024-06-19). AlphaMissense: likely benign (0.0845); Very rare (popmax 0.00224%, eas).

How common is ARNT p.Arg472Gln (c.1415G>A) in the general population?

ARNT p.Arg472Gln (c.1415G>A) is very rare (popmax 0.00224%, eas) (gnomAD).

What do computational predictors say about ARNT p.Arg472Gln (c.1415G>A)?

AlphaMissense predicts likely benign (score 0.0845) — an in-silico prediction, not a clinical call.

ARNT p.Arg472Gln

c.1415G>A · VCV3315901

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0845 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00224%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0845	likely benign
REVEL	0.17	moderately benign-leaning
SaProt	LLR -5.83	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6	GERP 2, phastCons 1
Regional constraint	o/e 0.87	unconstrained · MANE · 11 kb · p 0.011 · regional, not allelic
Overall
CADD	23.7	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 0.00224% East Asian · 1/44,712 alleles

Filtering AF 0.000366% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000137%

Overall 0.000621% 10/1,609,116 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00224%	44,712
South Asian	0.00221%	45,317
Remaining individualsnot grpmax-eligible	0.0016%	62,378
Finnishnot grpmax-eligible	0.00158%	63,242
African / African-American	0.00136%	73,302
European (non-Finnish)	0.000339%	294,738

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: ARNT
Protein: p.Arg472Gln
Coding: c.1415G>A
MANE Select: NM_001668
Type: single nucleotide variant
Location: chr1:150818010 (GRCh38)
Gene constraint: LOEUF 0.387 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 56.53 · 44 PDB
Residue 472: the 'disordered' region

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

Similar variants

ARNT p.Asp511Asn Benign/Likely benign ★★ same type
ARNT p.Ala107Gly Uncertain significance ★ ⚠ same type
ARNT p.Ala20Pro Uncertain significance ★ ⚠ same type
ARNT p.Ala687Val Uncertain significance ★ ⚠ same type
ARNT p.Ala84Thr Uncertain significance ★ ⚠ same type
ARNT p.Arg235His Uncertain significance ★ ⚠ same type
ARNT p.Arg43Trp Uncertain significance ★ ⚠ same type
ARNT p.Arg481Lys 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/arnt-p-arg472gln (accessed [today's date]).

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