Is MAX p.Arg47= (c.141G>A) pathogenic?

MAX p.Arg47= (c.141G>A) is classified Benign/Likely benign in MAX (ClinVar, Multiple submitters, 4 submitters; last evaluated 2026-06-08). Very rare (popmax 0.00017%, nfe); Associated with hereditary neoplastic syndrome.

What condition is associated with MAX p.Arg47= (c.141G>A)?

MAX p.Arg47= (c.141G>A) is associated with hereditary neoplastic syndrome, pheochromocytoma, hereditary pheochromocytoma-paraganglioma (ClinVar).

How common is MAX p.Arg47= (c.141G>A) in the general population?

MAX p.Arg47= (c.141G>A) is very rare (popmax 0.00017%, nfe) (gnomAD).

MAX p.Arg47=

c.141G>A · rs768413473 · VCV1772229

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00017%, nfe)

Conditions

hereditary neoplastic syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.3	GERP -0.06, phastCons 1
Overall
CADD	11.78	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00017% European (non-Finnish) · 2/1,176,978 alleles

Filtering AF 2.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000124% 2/1,610,840 alleles · very rare exomes 2/1,458,522 · genomes 0/152,318 · joint denominator

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: MAX
Protein: p.Arg47=
Coding: c.141G>A
MANE Select: NM_002382
dbSNP: rs768413473
Type: single nucleotide variant
Location: chr14:65093738 (GRCh38)
Gene constraint: LOEUF 0.288 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 82.07 · 12 PDB
Residue 47: the bhlh domain; a UniProt-annotated variant site (in pcc; does not repress myc transcriptional activity); a UniProt-annotated variant site (in pcc; uncertain significance; somatic mutation); an α-helix

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

Disease context

hereditary neoplastic syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: pheochromocytoma hereditary pheochromocytoma-paraganglioma

Similar variants

MAX p.Arg47Gln Uncertain significance ★★ ⚠ same residue
MAX p.Arg47Trp Uncertain significance ★★ ⚠ same residue
MAX p.Arg47Gly Uncertain significance ★ ⚠ 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

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-arg47 (accessed [today's date]).

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