Is MYC p.Pro246= (c.738G>A) pathogenic?

MYC p.Pro246= (c.738G>A) is classified Benign in MYC (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-09-06). Common (popmax 9.31%, eas) — too common for a highly-penetrant pathogenic allele; Associated with MYC-related disorder.

What condition is associated with MYC p.Pro246= (c.738G>A)?

MYC p.Pro246= (c.738G>A) is associated with MYC-related disorder (ClinVar).

MYC p.Pro246=

Q: How common is MYC p.Pro246= (c.738G>A) in the general population?

MYC p.Pro246= (c.738G>A) is common (popmax 9.31%, eas) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.738G>A · rs2070582 · VCV3057137

Benign No assertion criteria

Classification

Benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Common

common (popmax 9.31%, eas) — too common for a highly-penetrant pathogenic allele

Conditions

MYC-related disorder

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 -0.074	GERP -3.5, phastCons 0.13
Overall
CADD	5.3	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 9.31% East Asian · 4,167/44,764 alleles

Filtering AF 9.07% ClinGen BA1/BS1 input FAF95, joint · FAF99 8.98%

Overall 2.9% 46,077/1,588,556 alleles · common exomes 39,085/1,436,360 · genomes 6,992/152,196 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	9.31%	11
African / African-American	8.95%	11
Finnishnot grpmax-eligible	6.09%	16
Middle Eastern	5.81%	17
Ashkenazi Jewishnot grpmax-eligible	4.96%	20
South Asian	4.94%	20
Remaining individualsnot grpmax-eligible	3.23%	31
European (non-Finnish)	1.96%	51
Admixed American	1.51%	66
Amishnot grpmax-eligible	0.659%	152

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.Pro246=
Coding: c.738G>A
MANE Select: NM_002467
dbSNP: rs2070582
Type: single nucleotide variant
Location: chr8:127738955 (GRCh38)
Gene constraint: LOEUF 0.128 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 61.38 · 25 PDB
Residue 246: the 'disordered' region

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

Disease context

MYC-related disorder

Similar variants

MYC p.Gln146= Likely benign 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
MYC p.Ala224Val 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-pro246 (accessed [today's date]).

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