Is MAX p.Glu10Lys (c.28G>A) pathogenic?

MAX p.Glu10Lys (c.28G>A) is classified Uncertain significance in MAX (ClinVar, Single submitter, 1 submitter; last evaluated 2023-09-25). AlphaMissense: likely pathogenic (0.9666); Absent from gnomAD v4.1; Associated with hereditary neoplastic syndrome.

What condition is associated with MAX p.Glu10Lys (c.28G>A)?

MAX p.Glu10Lys (c.28G>A) is associated with hereditary neoplastic syndrome (ClinVar).

How common is MAX p.Glu10Lys (c.28G>A) in the general population?

MAX p.Glu10Lys (c.28G>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about MAX p.Glu10Lys (c.28G>A)?

AlphaMissense predicts likely pathogenic (score 0.9666) — an in-silico prediction, not a clinical call.

MAX p.Glu10Lys

c.28G>A · rs2139976890 · VCV3222155

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9666 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

hereditary neoplastic syndrome

Computational evidence

Protein change
AlphaMissense	0.9666	likely pathogenic
REVEL	0.519	indeterminate
SaProt	LLR -7.58	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call.
Splicing
SpliceAI	Δ0.31	donor gain · deltas
Constraint at this position
Conservation	phyloP 7.5	GERP -0.39, phastCons 1
Regional constraint	o/e 0.56	unconstrained · MANE · 8,551 bp · p 0.0042 · regional, not allelic
Overall
CADD	28.1	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

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.Glu10Lys
Coding: c.28G>A
MANE Select: NM_002382
dbSNP: rs2139976890
Type: single nucleotide variant
Location: chr14:65102312 (GRCh38)
Gene constraint: LOEUF 0.288 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 82.07 · 12 PDB
Residue 10: 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.Glu10Asp 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
MAX p.Gln97Ter 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-glu10lys (accessed [today's date]).

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