MDC1 p.Pro1245=
c.3735C>T · VCV4873354
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00269%, afr)
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 -16 | |
| Overall | ||
| CADD | 0.624 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00269%
African / African-American · 2/74,282 alleles
Filtering AF
0.000447%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000167%
Overall
0.000124%
2/1,610,798 alleles · very rare
exomes 0/1,460,054 · genomes 2/150,744 · 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
- MDC1
- Protein
- p.Pro1245=
- Coding
- c.3735C>T
- MANE Select
- NM_014641
- Type
- single nucleotide variant
- Location
- chr6:30705448 (GRCh38)
- Gene constraint
- LOEUF 0.648 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 40.39 · 12 PDB
- Residue 1245
- the 'disordered' region; the 'interaction with the prkdc complex' region
Similar variants
- MDC1 p.Gln1258= Likely benign ★★ same type
- MDC1 p.Leu1207Pro Likely benign ★★ same type
- MDC1 p.Ser1276= Benign/Likely benign ★★ same type
- MDC1 p.Thr1261= Likely benign ★★ same type
- MDC1 p.Arg1882Ter Pathogenic ★ same type
- MDC1 p.Arg1993Ter Pathogenic ★ same type
- MDC1 p.Met1Leu Pathogenic ★ same type
- MDC1 p.Ala1017Thr Uncertain significance ★ ⚠ same type
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/mdc1-p-pro1245 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown