Is MAX p.Arg90Gln (c.269G>A) pathogenic?

MAX p.Arg90Gln (c.269G>A) is classified Uncertain significance in MAX (ClinVar, Multiple submitters, 4 submitters; last evaluated 2025-11-04). AlphaMissense: likely benign (0.2277); Very rare (popmax 0.00167%, amr); Associated with hereditary neoplastic syndrome.

What condition is associated with MAX p.Arg90Gln (c.269G>A)?

MAX p.Arg90Gln (c.269G>A) is associated with hereditary neoplastic syndrome, pheochromocytoma, hereditary pheochromocytoma-paraganglioma (ClinVar).

How common is MAX p.Arg90Gln (c.269G>A) in the general population?

MAX p.Arg90Gln (c.269G>A) is very rare (popmax 0.00167%, amr) (gnomAD).

What do computational predictors say about MAX p.Arg90Gln (c.269G>A)?

AlphaMissense predicts likely benign (score 0.2277) — an in-silico prediction, not a clinical call.

MAX p.Arg90Gln

c.269G>A · rs876659562 · VCV485702

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

AlphaMissense

likely benign

0.2277 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00167%, amr)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

hereditary neoplastic syndrome

Computational evidence

Protein change
AlphaMissense	0.2277	likely benign
REVEL	0.638	indeterminate
SaProt	LLR -10.76	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 0.97, phastCons 1
Regional constraint	o/e 0.64	unconstrained · MANE · 17 kb · p 1.3e-05 · regional, not allelic
Overall
CADD	23.8	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

Grpmax group 0.00167% Admixed American · 1/60,028 alleles

Filtering AF 2.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000186% 3/1,614,206 alleles · very rare exomes 3/1,461,894 · genomes 0/152,312 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00167%	60,028
European (non-Finnish)	0.000169%	590,016

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.Arg90Gln
Coding: c.269G>A
MANE Select: NM_002382
dbSNP: rs876659562
Type: single nucleotide variant
Location: chr14:65077939 (GRCh38)
Gene constraint: LOEUF 0.288 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 82.07 · 12 PDB
Residue 90: a UniProt-annotated variant site (in pcc; does not repress myc transcriptional activity); a UniProt-annotated variant site (in pcc; uncertain significance); the 'leucine-zipper' region; 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

Also linked: pheochromocytoma hereditary pheochromocytoma-paraganglioma

Similar variants

MAX p.Arg90Trp Uncertain significance ★★ ⚠ same residue
MAX p.Arg90= Likely benign ★★ same residue
MAX p.Arg90Leu Uncertain significance ★ ⚠ same residue
MAX p.Arg90Pro 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-arg90gln (accessed [today's date]).

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