Is MED12 p.Pro342= (c.1026C>T) pathogenic?

MED12 p.Pro342= (c.1026C>T) is classified Likely benign in MED12 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-10-23). Very rare (popmax 0.00346%, afr); Associated with FG syndrome.

What condition is associated with MED12 p.Pro342= (c.1026C>T)?

MED12 p.Pro342= (c.1026C>T) is associated with FG syndrome (ClinVar).

How common is MED12 p.Pro342= (c.1026C>T) in the general population?

MED12 p.Pro342= (c.1026C>T) is very rare (popmax 0.00346%, afr) (gnomAD).

MED12 p.Pro342=

c.1026C>T · rs2092289951 · VCV2877424

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00346%, afr)

Conditions

FG syndrome

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 -0.13	GERP -4.1, phastCons 0.44
Overall
CADD	8.116	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00346% African / African-American · 2/57,752 alleles

Filtering AF 0.000574% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000215%

Overall 0.000248% 3/1,211,416 alleles · very rare exomes 3/1,097,812 · genomes 0/113,604 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00346%	28,876
European (non-Finnish)	0.000112%	895,327

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.Pro342=
Coding: c.1026C>T
MANE Select: NM_005120
dbSNP: rs2092289951
Type: single nucleotide variant
Location: chrX:71121741 (GRCh38)
Structure: AlphaFold pLDDT 65.80 · 3 PDB
Residue 342: the 'disordered' region; a UniProt-annotated variant site (in hdkr)

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

Disease context

FG syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

MED12 p.Pro342Leu Likely benign ★ same residue
OPA1 p.His342Arg Uncertain significance ★ same residue
MED12 c.6408+1G>A Pathogenic/Likely pathogenic ★★ same condition
MED12 p.Arg1295Cys Pathogenic/Likely pathogenic ★★ ⚠ same condition
MED12 p.Arg1295His Pathogenic ★★ same condition
MED12 p.Arg1357His Pathogenic/Likely pathogenic ★★ ⚠ same condition
MED12 p.Arg296Gln Pathogenic/Likely pathogenic ★★ ⚠ same condition
MED12 p.Arg961Trp Pathogenic/Likely 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/med12-p-pro342 (accessed [today's date]).

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