Is MAX p.Phe43= (c.129T>C) pathogenic?

MAX p.Phe43= (c.129T>C) is classified Likely benign in MAX (ClinVar, Single submitter, 1 submitter; last evaluated 2025-10-27). Absent from gnomAD v4.1; Associated with hereditary neoplastic syndrome.

What condition is associated with MAX p.Phe43= (c.129T>C)?

MAX p.Phe43= (c.129T>C) is associated with hereditary neoplastic syndrome (ClinVar).

How common is MAX p.Phe43= (c.129T>C) in the general population?

MAX p.Phe43= (c.129T>C) is absent from gnomAD v4.1 (gnomAD).

MAX p.Phe43=

c.129T>C · VCV4645780

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

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 6.2	GERP 0.81, phastCons 1
Overall
CADD	11.73	PHRED · no single calibrated threshold — expert panels disagree

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.Phe43=
Coding: c.129T>C
MANE Select: NM_002382
Type: single nucleotide variant
Location: chr14:65093750 (GRCh38)
Gene constraint: LOEUF 0.288 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 82.07 · 12 PDB
Residue 43: 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-phe43 (accessed [today's date]).

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