Is MAX p.Arg152Gly (c.454A>G) pathogenic?

MAX p.Arg152Gly (c.454A>G) is classified Uncertain significance in MAX (ClinVar, Single submitter, 1 submitter; last evaluated 2023-02-10). AlphaMissense: ambiguous (0.4097); Absent from gnomAD v4.1; Associated with hereditary neoplastic syndrome.

What condition is associated with MAX p.Arg152Gly (c.454A>G)?

MAX p.Arg152Gly (c.454A>G) is associated with hereditary neoplastic syndrome (ClinVar).

How common is MAX p.Arg152Gly (c.454A>G) in the general population?

MAX p.Arg152Gly (c.454A>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about MAX p.Arg152Gly (c.454A>G)?

AlphaMissense predicts ambiguous (score 0.4097) — an in-silico prediction, not a clinical call.

MAX p.Arg152Gly

c.454A>G · rs2504172800 · VCV2453895

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4097 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense no call

Conditions

hereditary neoplastic syndrome

Computational evidence

Protein change
AlphaMissense	0.4097	ambiguous
REVEL	0.813	moderately pathogenic-leaning
SaProt	LLR -9.12	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 4.2	GERP 0.83, phastCons 1
Regional constraint	o/e 0.64	unconstrained · MANE · 17 kb · p 1.3e-05 · regional, not allelic
Overall
CADD	28.8	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.Arg152Gly
Coding: c.454A>G
MANE Select: NM_002382
dbSNP: rs2504172800
Type: single nucleotide variant
Location: chr14:65076505 (GRCh38)
Gene constraint: LOEUF 0.288 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 82.07 · 12 PDB
Residue 152: 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

Similar variants

MAX p.Arg152= Likely benign ★★ same residue
MAX p.Arg152Ser 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.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-arg152gly (accessed [today's date]).

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