Is MED12 p.Pro152= (c.456T>C) pathogenic?

MED12 p.Pro152= (c.456T>C) is classified Likely benign in MED12 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-10-20). Very rare (popmax 0.00217%, amr); Associated with familial thoracic aortic aneurysm and aortic dissection.

What condition is associated with MED12 p.Pro152= (c.456T>C)?

MED12 p.Pro152= (c.456T>C) is associated with familial thoracic aortic aneurysm and aortic dissection (ClinVar).

How common is MED12 p.Pro152= (c.456T>C) in the general population?

MED12 p.Pro152= (c.456T>C) is very rare (popmax 0.00217%, amr) (gnomAD).

MED12 p.Pro152=

Q: How is Familial thoracic aortic aneurysm and aortic dissection inherited?

Typically Autosomal dominant (Orphanet). A genetic counselor can assess individual risk for a family.

c.456T>C · rs2519663682 · VCV1741563

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00217%, amr)

Conditions

familial thoracic aortic aneurysm and aortic dissection

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 0.33	GERP -0.32, phastCons 1
Overall
CADD	11.8	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00217% Admixed American · 1/46,033 alleles

Overall 9.11e-05% 1/1,097,958 alleles · very rare

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: MED12
Protein: p.Pro152=
Coding: c.456T>C
MANE Select: NM_005120
dbSNP: rs2519663682
Type: single nucleotide variant
Location: chrX:71120073 (GRCh38)
Structure: AlphaFold pLDDT 65.80 · 3 PDB
Residue 152: a UniProt-annotated variant site (in hdkr)

Full MED12 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

familial thoracic aortic aneurysm and aortic dissection — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Familial thoracic aortic aneurysm and aortic dissection (Orphanet):

Inheritance: Autosomal dominant
Onset: Adolescent, Adult, Childhood

Similar variants

OPA1 p.Ile152Asn Uncertain significance ★★ ⚠ same residue
MED12 p.Pro152Ser Uncertain significance ★ ⚠ same residue
MED12 p.Arg1295His Pathogenic ★★ same condition
MED12 p.Arg961Trp Pathogenic/Likely pathogenic ★★ ⚠ same condition
MED12 p.Gln1974Ter Pathogenic ★★ same condition
MED12 c.4048-3C>T Uncertain significance ★★ same condition
MED12 c.5401-3C>A Uncertain significance ★★ same condition
MED12 c.736-3T>C Uncertain significance ★★ 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/med12-p-pro152 (accessed [today's date]).

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