Is MAX p.Leu94Pro (c.281T>C) pathogenic?

MAX p.Leu94Pro (c.281T>C) is classified Uncertain significance in MAX (ClinVar, Single submitter, 1 submitter; last evaluated 2021-11-20). AlphaMissense: likely pathogenic (0.996); Absent from gnomAD v4.1; Associated with hereditary neoplastic syndrome.

What condition is associated with MAX p.Leu94Pro (c.281T>C)?

MAX p.Leu94Pro (c.281T>C) is associated with hereditary neoplastic syndrome (ClinVar).

How common is MAX p.Leu94Pro (c.281T>C) in the general population?

MAX p.Leu94Pro (c.281T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about MAX p.Leu94Pro (c.281T>C)?

AlphaMissense predicts likely pathogenic (score 0.996) — an in-silico prediction, not a clinical call.

MAX p.Leu94Pro

c.281T>C · rs2504194614 · VCV1796437

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.996 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

hereditary neoplastic syndrome

Computational evidence

Protein change
AlphaMissense	0.996	likely pathogenic
REVEL	0.869	moderately pathogenic-leaning
SaProt	LLR -15.09	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 1.9, phastCons 1
Regional constraint	o/e 0.64	unconstrained · MANE · 17 kb · p 1.3e-05 · regional, not allelic
Overall
CADD	31.0	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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.Leu94Pro
Coding: c.281T>C
MANE Select: NM_002382
dbSNP: rs2504194614
Type: single nucleotide variant
Location: chr14:65077927 (GRCh38)
Gene constraint: LOEUF 0.288 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 82.07 · 12 PDB
Residue 94: 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

Similar variants

MAX p.Leu94Ile Uncertain significance ★★ ⚠ same residue
MAX p.Leu94Phe Uncertain significance ★★ ⚠ same residue
MAX p.Leu94Val Uncertain significance ★★ ⚠ same residue
MAX p.Leu94= Likely 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

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-leu94pro (accessed [today's date]).

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