Is MYC p.Pro72Ser (c.214C>T) pathogenic?

MYC p.Pro72Ser (c.214C>T) is classified Pathogenic in MYC (ClinVar, No assertion criteria, 1 submitter; last evaluated 1993-09-01). AlphaMissense: likely pathogenic (0.9903); Very rare (popmax 6.21e-05%); Associated with Burkitt lymphoma.

What condition is associated with MYC p.Pro72Ser (c.214C>T)?

MYC p.Pro72Ser (c.214C>T) is associated with Burkitt lymphoma (ClinVar).

How common is MYC p.Pro72Ser (c.214C>T) in the general population?

MYC p.Pro72Ser (c.214C>T) is very rare (popmax 6.21e-05%) (gnomAD).

How is Burkitt lymphoma inherited?

Typically Not applicable (Orphanet). A genetic counselor can assess individual risk for a family.

What do computational predictors say about MYC p.Pro72Ser (c.214C>T)?

AlphaMissense predicts likely pathogenic (score 0.9903) — an in-silico prediction, not a clinical call.

MYC p.Pro72Ser

c.214C>T · rs28933407 · VCV12574

Pathogenic No assertion criteria

Classification

Pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9903 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 6.21e-05%)

Conditions

Burkitt lymphoma

Computational evidence

Protein change
AlphaMissense	0.9903	likely pathogenic ✓ concordant with ClinVar · top 6% in MYC
REVEL	0.445	indeterminate
SaProt	—	withheld · numbering disagrees past residue 7 · why
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.5	GERP 2.2, phastCons 1
Regional constraint	o/e 0.18	constrained · MANE · 40 bp · p 0.0008 · regional, not allelic
Overall
CADD	29.1	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL is an independent agreement signal.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM P57S vs ClinVar P72S) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 6.21e-05%

Overall 6.21e-05% 1/1,610,880 alleles · very rare exomes 0/1,458,582 · genomes 1/152,298 · 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: MYC
Protein: p.Pro72Ser
Coding: c.214C>T
MANE Select: NM_002467
dbSNP: rs28933407
Type: single nucleotide variant
Location: chr8:127738431 (GRCh38)
Gene constraint: LOEUF 0.128 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 61.38 · 25 PDB

Full MYC gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Burkitt lymphoma — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Burkitt lymphoma (Orphanet):

Inheritance: Not applicable
Onset: All ages
Prevalence: 1-9 / 1 000 000 (Europe)

Similar variants

MYC p.Asn101Thr Pathogenic ⚠ same condition
MYC p.Glu54Asp Pathogenic ⚠ same condition
MYC p.Asn26Ser Uncertain significance ★★ ⚠ same type
MYC p.Gln48= Benign ★★ same type
MYC p.Phe22Leu Benign/Likely benign ★★ same type
MYC p.Ser362Phe Benign/Likely benign ★★ same type
MYC p.Thr73Ala Pathogenic ★ same type
MYC c.30+4A>T Uncertain significance ★ same type

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/myc-p-pro72ser (accessed [today's date]).

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