Is MAX p.Arg60Gln (c.179G>A) pathogenic?

MAX p.Arg60Gln (c.179G>A) is classified Conflicting classifications of pathogenicity in MAX (ClinVar, Conflicting submitters, 6 submitters; last evaluated 2025-12-23). AlphaMissense: likely pathogenic (0.9996); Absent from gnomAD v4.1; Associated with MAX-related disorder.

What condition is associated with MAX p.Arg60Gln (c.179G>A)?

MAX p.Arg60Gln (c.179G>A) is associated with MAX-related disorder, hereditary pheochromocytoma-paraganglioma, polydactyly-macrocephaly syndrome (ClinVar).

How common is MAX p.Arg60Gln (c.179G>A) in the general population?

MAX p.Arg60Gln (c.179G>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about MAX p.Arg60Gln (c.179G>A)?

AlphaMissense predicts likely pathogenic (score 0.9996) — an in-silico prediction, not a clinical call.

MAX p.Arg60Gln

c.179G>A · rs2063106020 · VCV958620

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 6 submitters

AlphaMissense

likely pathogenic

0.9996 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

MAX-related disorder

Computational evidence

Protein change
AlphaMissense	0.9996	likely pathogenic · top 8% in MAX
REVEL	0.897	moderately pathogenic-leaning
SaProt	LLR -13.62	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 0.97, phastCons 1
Regional constraint	o/e 0.64	unconstrained · MANE · 17 kb · p 1.3e-05 · regional, not allelic
Overall
CADD	32.0	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.Arg60Gln
Coding: c.179G>A
MANE Select: NM_002382
dbSNP: rs2063106020
Type: single nucleotide variant
Location: chr14:65078029 (GRCh38)
Gene constraint: LOEUF 0.288 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 82.07 · 12 PDB
Residue 60: the bhlh domain; a UniProt-annotated variant site (in pcc; does not repress myc transcriptional activity); a UniProt-annotated variant site (in pdmcs; likely pathogenic; results in increased myc transcriptional activity; increased interaction with myc; decreased max binding to its target e-box sequences); an α-helix

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

Disease context

MAX-related disorder

Also linked: hereditary pheochromocytoma-paraganglioma polydactyly-macrocephaly syndrome

Similar variants

MAX p.Arg60Trp 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
MAX p.Gln19Ter Pathogenic/Likely pathogenic ★★ same condition
MAX p.Gln91Ter 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-arg60gln (accessed [today's date]).

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