MDC1 p.Pro1693=
c.5079G>A · rs187724951 · VCV747196
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
rare (popmax 0.12%, eas)
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 -1.1 | |
| Overall | ||
| CADD | 1.168 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.12%
East Asian · 54/44,870 alleles
Filtering AF
0.0947%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0855%
Overall
0.00923%
149/1,613,858 alleles · rare
exomes 136/1,461,848 · genomes 13/152,010 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.12% | 831 |
| South Asian | 0.0329% | 3,036 |
| European (non-Finnish) | 0.00509% | 19,666 |
| Remaining individualsnot grpmax-eligible | 0.0048% | 20,831 |
| Finnishnot grpmax-eligible | 0.00156% | 64,004 |
| African / African-American | 0.00133% | 74,922 |
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.Pro1693=
- Coding
- c.5079G>A
- MANE Select
- NM_014641
- dbSNP
- rs187724951
- Type
- single nucleotide variant
- Location
- chr6:30704104 (GRCh38)
- Gene constraint
- LOEUF 0.648 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 40.39 · 12 PDB
- Residue 1693
- the 'disordered' region
Similar variants
- MDC1 p.Pro1693Ser Uncertain significance ★ ⚠ same residue
- MDC1 p.Pro1693Leu Likely benign ★ same residue
- 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
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-pro1693 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown