Is MAX p.Arg156Trp (c.466C>T) pathogenic?

MAX p.Arg156Trp (c.466C>T) is classified Uncertain significance in MAX (ClinVar, Multiple submitters, 4 submitters; last evaluated 2025-12-23). AlphaMissense: likely pathogenic (0.573); Very rare (popmax 0.00223%, eas); Associated with hereditary neoplastic syndrome.

What condition is associated with MAX p.Arg156Trp (c.466C>T)?

MAX p.Arg156Trp (c.466C>T) is associated with hereditary neoplastic syndrome, pheochromocytoma, hereditary pheochromocytoma-paraganglioma (ClinVar).

How common is MAX p.Arg156Trp (c.466C>T) in the general population?

MAX p.Arg156Trp (c.466C>T) is very rare (popmax 0.00223%, eas) (gnomAD).

What do computational predictors say about MAX p.Arg156Trp (c.466C>T)?

AlphaMissense predicts likely pathogenic (score 0.573) — an in-silico prediction, not a clinical call.

MAX p.Arg156Trp

c.466C>T · rs768360710 · VCV647774

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

AlphaMissense

likely pathogenic

0.573 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00223%, eas)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

hereditary neoplastic syndrome

Computational evidence

Protein change
AlphaMissense	0.573	likely pathogenic
REVEL	0.687	pathogenic-leaning
SaProt	LLR -12.49	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 12	GERP 1.9, phastCons 1
Regional constraint	o/e 0.64	unconstrained · MANE · 17 kb · p 1.3e-05 · regional, not allelic
Overall
CADD	34.0	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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 0.00223% East Asian · 1/44,880 alleles

Filtering AF 7.9e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 5.4e-05%

Overall 0.000372% 6/1,613,444 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00223%	44,880
African / African-American	0.00134%	74,872
European (non-Finnish)	0.000339%	295,004

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.Arg156Trp
Coding: c.466C>T
MANE Select: NM_002382
dbSNP: rs768360710
Type: single nucleotide variant
Location: chr14:65076493 (GRCh38)
Gene constraint: LOEUF 0.288 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 82.07 · 12 PDB
Residue 156: a UniProt-annotated variant site (in pcc; does not repress myc transcriptional activity); a UniProt-annotated variant site (in pcc; uncertain significance); the 'disordered' region

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.Arg156Gln Uncertain significance ★★ ⚠ same residue
MAX p.Arg156Gly 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

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-arg156trp (accessed [today's date]).

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