Is MAX p.Gln112= (c.336G>A) pathogenic?

MAX p.Gln112= (c.336G>A) is classified Likely benign in MAX (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-03-26). Very rare (popmax 0.0011%, sas); Associated with hereditary neoplastic syndrome.

What condition is associated with MAX p.Gln112= (c.336G>A)?

MAX p.Gln112= (c.336G>A) is associated with hereditary neoplastic syndrome, hereditary pheochromocytoma-paraganglioma (ClinVar).

How common is MAX p.Gln112= (c.336G>A) in the general population?

MAX p.Gln112= (c.336G>A) is very rare (popmax 0.0011%, sas) (gnomAD).

MAX p.Gln112=

c.336G>A · rs1595127306 · VCV823675

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.0011%, sas)

Conditions

hereditary neoplastic syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.391	indeterminate
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 1.9, phastCons 1
Overall
CADD	13.02	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0011% South Asian · 1/91,064 alleles

Filtering AF 0.000124% ClinGen BA1/BS1 input FAF95, joint · FAF99 9e-05%

Overall 0.000372% 6/1,614,122 alleles · very rare exomes 6/1,461,878 · genomes 0/152,244 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0011%	91,064
European (non-Finnish)	0.000424%	236,004

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.Gln112=
Coding: c.336G>A
MANE Select: NM_002382
dbSNP: rs1595127306
Type: single nucleotide variant
Location: chr14:65076623 (GRCh38)
Gene constraint: LOEUF 0.288 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 82.07 · 12 PDB
Residue 112: 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: hereditary pheochromocytoma-paraganglioma

Similar variants

MAX p.Gln112Arg Uncertain significance ★ ⚠ same residue
MAX p.Gln112His Uncertain significance ★ ⚠ same residue
MAX p.Gln112Ter 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

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-gln112 (accessed [today's date]).

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