Is ARNT2 p.Val192Met (c.574G>A) pathogenic?

ARNT2 p.Val192Met (c.574G>A) is classified Uncertain significance in ARNT2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-10-08). AlphaMissense: likely benign (0.1049); Ultra-rare (popmax 0.0936%, eas).

How common is ARNT2 p.Val192Met (c.574G>A) in the general population?

ARNT2 p.Val192Met (c.574G>A) is ultra-rare (popmax 0.0936%, eas) (gnomAD).

What do computational predictors say about ARNT2 p.Val192Met (c.574G>A)?

AlphaMissense predicts likely benign (score 0.1049) — an in-silico prediction, not a clinical call.

ARNT2 p.Val192Met

c.574G>A · rs201803008 · VCV1416200

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1049 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0936%, eas)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1049	likely benign
REVEL	0.103	moderately benign-leaning
SaProt	LLR -12.29	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 1.9, phastCons 1
Regional constraint	o/e 0.87	unconstrained · MANE · 88 kb · p 0.02 · regional, not allelic
Overall
CADD	27.3	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 0.0936% East Asian · 42/44,890 alleles

Filtering AF 0.0711% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0632%

Overall 0.00638% 103/1,614,184 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0936%	1,069
South Asian	0.0165%	6,071
European (non-Finnish)	0.00373%	26,819
Admixed American	0.00167%	60,030
Remaining individualsnot grpmax-eligible	0.0016%	62,510

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: ARNT2
Protein: p.Val192Met
Coding: c.574G>A
MANE Select: NM_014862
dbSNP: rs201803008
Type: single nucleotide variant
Location: chr15:80475175 (GRCh38)
Gene constraint: LOEUF 0.498 · pLI 0.94 (gnomAD)
Structure: AlphaFold pLDDT 59.49
Residue 192: the pas 1 domain

Full ARNT2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

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ARNT2 p.Asp705Tyr Uncertain significance ★★ ⚠ same type
ARNT2 p.Gln520Arg Uncertain significance ★★ ⚠ same type
ARNT2 p.Gly472Ser Uncertain significance ★★ ⚠ same type
ARNT2 p.Gly546Arg Uncertain significance ★★ ⚠ same type
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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/arnt2-p-val192met (accessed [today's date]).

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