MED12 p.Phe2137=
c.6411C>T · rs1213131764 · VCV2868703
Benign
Single submitter
Classification
Benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00529%, sas)
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 1.3 | GERP -0.95, phastCons 1 |
| Overall | ||
| CADD | 11.33 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00529%
South Asian · 3/56,689 alleles
Filtering AF
0.0014%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000689%
Overall
0.000248%
3/1,208,266 alleles · very rare
exomes 2/1,097,287 · genomes 1/110,979 · 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.Phe2137=
- Coding
- c.6411C>T
- MANE Select
- NM_005120
- dbSNP
- rs1213131764
- Type
- single nucleotide variant
- Location
- chrX:71141885 (GRCh38)
- Structure
- AlphaFold pLDDT 65.80 · 3 PDB
- Residue 2137
- the 'disordered' region; a UniProt-annotated variant site (in hdkr)
Similar variants
- 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
- MED12 p.Asn1007Ser Pathogenic/Likely pathogenic ★★ ⚠ same condition
- MED12 c.2542-4T>G 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-phe2137 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown