Is MAX p.Gln54Arg (c.161A>G) pathogenic?

MAX p.Gln54Arg (c.161A>G) is classified Uncertain significance in MAX (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-07). AlphaMissense: ambiguous (0.5078); Absent from gnomAD v4.1; Associated with hereditary pheochromocytoma-paraganglioma.

What condition is associated with MAX p.Gln54Arg (c.161A>G)?

MAX p.Gln54Arg (c.161A>G) is associated with hereditary pheochromocytoma-paraganglioma (ClinVar).

How common is MAX p.Gln54Arg (c.161A>G) in the general population?

MAX p.Gln54Arg (c.161A>G) is absent from gnomAD v4.1 (gnomAD).

How is Hereditary pheochromocytoma-paraganglioma inherited?

Typically Autosomal dominant (Orphanet). A genetic counselor can assess individual risk for a family.

What do computational predictors say about MAX p.Gln54Arg (c.161A>G)?

AlphaMissense predicts ambiguous (score 0.5078) — an in-silico prediction, not a clinical call.

MAX p.Gln54Arg

c.161A>G · rs2504402383 · VCV2009068

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5078 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense no call

Conditions

hereditary pheochromocytoma-paraganglioma

Computational evidence

Protein change
AlphaMissense	0.5078	ambiguous
REVEL	0.66	pathogenic-leaning
SaProt	LLR -9.63	tolerated
⇒ REVEL calls this damaging; SaProt does not; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 8	GERP 1.9, phastCons 1
Regional constraint	o/e 0.64	unconstrained · MANE · 17 kb · p 1.3e-05 · regional, not allelic
Overall
CADD	24.9	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: MAX
Protein: p.Gln54Arg
Coding: c.161A>G
MANE Select: NM_002382
dbSNP: rs2504402383
Type: single nucleotide variant
Location: chr14:65093718 (GRCh38)
Gene constraint: LOEUF 0.288 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 82.07 · 12 PDB
Residue 54: the bhlh domain; a UniProt-annotated variant site (in pcc; does not repress myc transcriptional activity); a turn

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

Disease context

hereditary pheochromocytoma-paraganglioma — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Hereditary pheochromocytoma-paraganglioma (Orphanet):

Inheritance: Autosomal dominant
Onset: Childhood
Prevalence: 1-9 / 1 000 000 (Worldwide)

Similar variants

MAX p.Gln54His Uncertain significance ★★ same residue
MAX p.Gln54= Likely benign ★ same residue
MAX c.295+1G>A Pathogenic ★★ same condition
MAX c.295+1G>T Pathogenic ★★ same condition
MAX p.Ala67Asp Pathogenic/Likely pathogenic ★★ same condition
MAX p.Arg33Ter Pathogenic ★★ same condition
MAX p.Arg75Ter Pathogenic ★★ same condition
MAX p.Gln19Ter Pathogenic/Likely pathogenic ★★ 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/max-p-gln54arg (accessed [today's date]).

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