Is MAX p.Asp119Asn (c.355G>A) pathogenic?

MAX p.Asp119Asn (c.355G>A) is classified Uncertain significance in MAX (ClinVar, Single submitter, 1 submitter; last evaluated 2023-06-14). AlphaMissense: likely benign (0.1387); Absent from gnomAD v4.1; Associated with hereditary pheochromocytoma-paraganglioma.

What condition is associated with MAX p.Asp119Asn (c.355G>A)?

MAX p.Asp119Asn (c.355G>A) is associated with hereditary pheochromocytoma-paraganglioma (ClinVar).

How common is MAX p.Asp119Asn (c.355G>A) in the general population?

MAX p.Asp119Asn (c.355G>A) is absent from gnomAD v4.1 (gnomAD).

How is Hereditary pheochromocytoma-paraganglioma inherited?

Typically Autosomal dominant (Orphanet). A genetic counselor can assess individual risk for a family.

What do computational predictors say about MAX p.Asp119Asn (c.355G>A)?

AlphaMissense predicts likely benign (score 0.1387) — an in-silico prediction, not a clinical call.

MAX p.Asp119Asn

c.355G>A · rs2139741082 · VCV3015166

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1387 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

hereditary pheochromocytoma-paraganglioma

Computational evidence

Protein change
AlphaMissense	0.1387	likely benign
REVEL	0.418	indeterminate
SaProt	LLR -4.97	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>G here scores Δ0.20 · evaluated, not missing
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	24.3	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: MAX
Protein: p.Asp119Asn
Coding: c.355G>A
MANE Select: NM_002382
dbSNP: rs2139741082
Type: single nucleotide variant
Location: chr14:65076604 (GRCh38)
Gene constraint: LOEUF 0.288 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 82.07 · 12 PDB
Residue 119: 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 pheochromocytoma-paraganglioma — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Hereditary pheochromocytoma-paraganglioma (Orphanet):

Inheritance: Autosomal dominant
Onset: Childhood
Prevalence: 1-9 / 1 000 000 (Worldwide)

Similar variants

MAX p.Asp119Gly Uncertain significance ★ ⚠ same residue
MAX p.Asp119Glu Uncertain significance ★★ ⚠ same residue
MAX p.Asp119= Benign ★ 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-asp119asn (accessed [today's date]).

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