Is MAX p.Glu69= (c.207A>G) pathogenic?

MAX p.Glu69= (c.207A>G) is classified Likely benign in MAX (ClinVar, Single submitter, 1 submitter; last evaluated 2024-03-20). Very rare (popmax 0.00446%, eas); Associated with hereditary neoplastic syndrome.

What condition is associated with MAX p.Glu69= (c.207A>G)?

MAX p.Glu69= (c.207A>G) is associated with hereditary neoplastic syndrome (ClinVar).

How common is MAX p.Glu69= (c.207A>G) in the general population?

MAX p.Glu69= (c.207A>G) is very rare (popmax 0.00446%, eas) (gnomAD).

MAX p.Glu69=

c.207A>G · VCV3293484

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00446%, eas)

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 1	GERP -3.2, phastCons 1
Overall
CADD	7.774	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00446% East Asian · 2/44,892 alleles

Filtering AF 0.000738% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000276%

Overall 0.000124% 2/1,614,068 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.Glu69=
Coding: c.207A>G
MANE Select: NM_002382
Type: single nucleotide variant
Location: chr14:65078001 (GRCh38)
Gene constraint: LOEUF 0.288 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 82.07 · 12 PDB
Residue 69: the bhlh domain; a UniProt-annotated variant site (in pcc; does not repress myc transcriptional activity); 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

Similar variants

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
MAX p.Gln97Ter Pathogenic ★★ same condition
MAX c.63+4C>T Uncertain significance ★★ 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-glu69 (accessed [today's date]).

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