Is MAX p.Ser121Thr (c.362G>C) pathogenic?

MAX p.Ser121Thr (c.362G>C) is classified Uncertain significance in MAX (ClinVar, Single submitter, 1 submitter; last evaluated 2025-10-21). AlphaMissense: likely benign (0.0872); Very rare (popmax 8.47e-05%, nfe); Associated with hereditary neoplastic syndrome.

What condition is associated with MAX p.Ser121Thr (c.362G>C)?

MAX p.Ser121Thr (c.362G>C) is associated with hereditary neoplastic syndrome (ClinVar).

How common is MAX p.Ser121Thr (c.362G>C) in the general population?

MAX p.Ser121Thr (c.362G>C) is very rare (popmax 8.47e-05%, nfe) (gnomAD).

What do computational predictors say about MAX p.Ser121Thr (c.362G>C)?

AlphaMissense predicts likely benign (score 0.0872) — an in-silico prediction, not a clinical call.

MAX p.Ser121Thr

c.362G>C · VCV4645770

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0872 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.47e-05%, nfe)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

hereditary neoplastic syndrome

Computational evidence

Protein change
AlphaMissense	0.0872	likely benign
REVEL	0.382	indeterminate
SaProt	LLR -6.42	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6	GERP 1.9, phastCons 1
Regional constraint	o/e 0.64	unconstrained · MANE · 17 kb · p 1.3e-05 · regional, not allelic
Overall
CADD	24.6	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

Grpmax group 8.47e-05% European (non-Finnish) · 1/1,179,994 alleles

Overall 6.2e-05% 1/1,614,050 alleles · very rare exomes 1/1,461,892 · genomes 0/152,158 · joint denominator

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.Ser121Thr
Coding: c.362G>C
MANE Select: NM_002382
Type: single nucleotide variant
Location: chr14:65076597 (GRCh38)
Gene constraint: LOEUF 0.288 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 82.07 · 12 PDB
Residue 121: 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 neoplastic syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

MAX p.Ser121= Benign/Likely benign ★★ same residue
MAX p.Ser121Arg 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
MAX p.Arg75Ter Pathogenic ★★ same condition
MAX p.Gln91Ter 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-ser121thr (accessed [today's date]).

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