Is MAX p.Arg152Ser (c.456G>C) pathogenic?

MAX p.Arg152Ser (c.456G>C) is classified Uncertain significance in MAX (ClinVar, Single submitter, 1 submitter; last evaluated 2022-07-12). AlphaMissense: likely pathogenic (0.7773); Very rare (popmax 8.47e-05%, nfe).

How common is MAX p.Arg152Ser (c.456G>C) in the general population?

MAX p.Arg152Ser (c.456G>C) is very rare (popmax 8.47e-05%, nfe) (gnomAD).

What do computational predictors say about MAX p.Arg152Ser (c.456G>C)?

AlphaMissense predicts likely pathogenic (score 0.7773) — an in-silico prediction, not a clinical call.

MAX p.Arg152Ser

c.456G>C · rs546006873 · VCV1878967

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7773 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.47e-05%, nfe)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.7773	likely pathogenic
REVEL	0.809	moderately pathogenic-leaning
SaProt	LLR -7.10	tolerated
⇒ AlphaMissense and REVEL call this damaging; SaProt does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6	GERP 1.9, phastCons 1
Regional constraint	o/e 0.64	unconstrained · MANE · 17 kb · p 1.3e-05 · regional, not allelic
Overall
CADD	26.6	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

Grpmax group 8.47e-05% European (non-Finnish) · 1/1,180,036 alleles

Overall 6.84e-05% 1/1,461,602 alleles · very rare

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.Arg152Ser
Coding: c.456G>C
MANE Select: NM_002382
dbSNP: rs546006873
Type: single nucleotide variant
Location: chr14:65076503 (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

Similar variants

MAX p.Arg152= Likely benign ★★ same residue
MAX p.Arg152Gly Uncertain significance ★ ⚠ same residue
MAX c.295+1G>A Pathogenic ★★ same type
MAX c.295+1G>T Pathogenic ★★ same type
MAX p.Ala67Asp Pathogenic/Likely pathogenic ★★ same type
MAX p.Arg33Ter Pathogenic ★★ same type
MAX p.Arg75Ter Pathogenic ★★ same type
MAX p.Gln19Ter Pathogenic/Likely pathogenic ★★ same type

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-arg152ser (accessed [today's date]).

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