MED12 p.Pro682=
c.2046T>C · VCV4733651
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.023%, mid)
Conditions
1
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 -1.7 | GERP 0.57 |
| Overall | ||
| CADD | 7.498 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.023%
Middle Eastern · 1/4,341 alleles
Overall
8.29e-05%
1/1,206,562 alleles · ultra-rare
exomes 1/1,092,633 · genomes 0/113,929 · 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
- MED12
- Protein
- p.Pro682=
- Coding
- c.2046T>C
- MANE Select
- NM_005120
- Type
- single nucleotide variant
- Location
- chrX:71124835 (GRCh38)
- Structure
- AlphaFold pLDDT 65.80 · 3 PDB
- Residue 682
- a UniProt-annotated variant site (in hdkr)
Similar variants
- MED12 p.Pro682Thr Likely benign ★ same residue
- OPA1 p.Arg682Lys Uncertain significance ★★ ⚠ same residue
- OPA1 p.Arg682Gly Uncertain significance ★ ⚠ same residue
- OPA1 p.Arg682Ser 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
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-pro682 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown