Is MED12 p.Pro337= (c.1011A>G) pathogenic?

MED12 p.Pro337= (c.1011A>G) is classified Likely benign in MED12 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-01-12). Absent from gnomAD v4.1; Associated with FG syndrome.

What condition is associated with MED12 p.Pro337= (c.1011A>G)?

MED12 p.Pro337= (c.1011A>G) is associated with FG syndrome (ClinVar).

How common is MED12 p.Pro337= (c.1011A>G) in the general population?

MED12 p.Pro337= (c.1011A>G) is absent from gnomAD v4.1 (gnomAD).

MED12 p.Pro337=

c.1011A>G · rs749348331 · VCV1461467

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

FG syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 0.89	GERP -0.11, phastCons 0.064
Overall
CADD	13.2	PHRED · no single calibrated threshold — expert panels disagree

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: MED12
Protein: p.Pro337=
Coding: c.1011A>G
MANE Select: NM_005120
dbSNP: rs749348331
Type: single nucleotide variant
Location: chrX:71121726 (GRCh38)
Structure: AlphaFold pLDDT 65.80 · 3 PDB
Residue 337: 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.Pro337Ser Uncertain significance ★ ⚠ same residue
OPA1 p.Tyr337Ter Pathogenic ★ same residue
OPA1 p.Tyr337= Likely benign ★ 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

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-pro337 (accessed [today's date]).

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