Is MDC1 p.Pro1286= (c.3858C>T) pathogenic?

MDC1 p.Pro1286= (c.3858C>T) is classified Likely benign in MDC1 (ClinVar, Single submitter, 1 submitter; last evaluated 2026-06-01). Absent from gnomAD v4.1.

How common is MDC1 p.Pro1286= (c.3858C>T) in the general population?

MDC1 p.Pro1286= (c.3858C>T) is absent from gnomAD v4.1 (gnomAD).

MDC1 p.Pro1286=

c.3858C>T · VCV4873353

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

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 -7.7
Overall
CADD	0.921	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: MDC1
Protein: p.Pro1286=
Coding: c.3858C>T
MANE Select: NM_014641
Type: single nucleotide variant
Location: chr6:30705325 (GRCh38)
Gene constraint: LOEUF 0.648 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 40.39 · 12 PDB
Residue 1286: the 'disordered' region; the 'interaction with the prkdc complex' region

Full MDC1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

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-pro1286 (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown