MED12 p.Pro49=
c.147T>A · rs774875020 · VCV696749
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
very rare (popmax 0.00798%, nfe)
Conditions
2
FG syndrome
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.054 | moderately benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP -0.96 | GERP 1, phastCons 0.007 |
| Overall | ||
| CADD | 11.0 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00798%
European (non-Finnish) · 71/889,784 alleles
Filtering AF
0.00645%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00592%
Overall
0.00662%
72/1,088,090 alleles · very rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.00798% | 12,532 |
| Remaining individualsnot grpmax-eligible | 0.00212% | 47,271 |
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.Pro49=
- Coding
- c.147T>A
- MANE Select
- NM_005120
- dbSNP
- rs774875020
- Type
- single nucleotide variant
- Location
- chrX:71119420 (GRCh38)
- Structure
- AlphaFold pLDDT 65.80 · 3 PDB
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 p.Gln1974Ter 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-pro49 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown