Is MAX p.Gln19= (c.57A>G) pathogenic?

MAX p.Gln19= (c.57A>G) is classified Conflicting classifications of pathogenicity in MAX (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2025-12-17). Ultra-rare (popmax 0.0165%, mid); Associated with hereditary neoplastic syndrome.

What condition is associated with MAX p.Gln19= (c.57A>G)?

MAX p.Gln19= (c.57A>G) is associated with hereditary neoplastic syndrome, hereditary pheochromocytoma-paraganglioma (ClinVar).

How common is MAX p.Gln19= (c.57A>G) in the general population?

MAX p.Gln19= (c.57A>G) is ultra-rare (popmax 0.0165%, mid) (gnomAD).

MAX p.Gln19=

c.57A>G · rs1395966308 · VCV463812

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0165%, mid)

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 3.4	GERP 0.3, phastCons 1
Overall
CADD	12.7	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0165% Middle Eastern · 1/6,056 alleles

Filtering AF 0.00177% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000892%

Overall 0.000373% 6/1,610,570 alleles · ultra-rare exomes 6/1,458,582 · genomes 0/151,988 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0165%	6,056
East Asian	0.00669%	14,952
African / African-American	0.00267%	37,403

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.Gln19=
Coding: c.57A>G
MANE Select: NM_002382
dbSNP: rs1395966308
Type: single nucleotide variant
Location: chr14:65101552 (GRCh38)
Gene constraint: LOEUF 0.288 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 82.07 · 12 PDB
Residue 19: 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.Gln19Ter Pathogenic/Likely pathogenic ★★ same residue
MAX p.Gln19His Uncertain significance ★★ ⚠ same residue
MAX p.Gln19Leu Conflicting classifications of pathogenicity ★ ⚠ same residue
MAX p.Gln19fs 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

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-gln19 (accessed [today's date]).

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