Is MDC1 p.Asp1966Val (c.5897A>T) pathogenic?

MDC1 p.Asp1966Val (c.5897A>T) is classified Uncertain significance in MDC1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-12-10). AlphaMissense: ambiguous (0.3763); Absent from gnomAD v4.1.

How common is MDC1 p.Asp1966Val (c.5897A>T) in the general population?

MDC1 p.Asp1966Val (c.5897A>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about MDC1 p.Asp1966Val (c.5897A>T)?

AlphaMissense predicts ambiguous (score 0.3763) — an in-silico prediction, not a clinical call.

MDC1 p.Asp1966Val

c.5897A>T · VCV3393984

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3763 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Computational evidence

Protein change
AlphaMissense	0.3763	ambiguous
REVEL	0.545	indeterminate
SaProt	LLR -8.54	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6.2	phastCons 1
Regional constraint	o/e 0.83	unconstrained · MANE · 15 kb · p 1.9e-17 · regional, not allelic
Overall
CADD	23.5	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

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.Asp1966Val
Coding: c.5897A>T
MANE Select: NM_014641
Type: single nucleotide variant
Location: chr6:30702846 (GRCh38)
Gene constraint: LOEUF 0.648 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 40.39 · 12 PDB
Residue 1966: the 'required for nuclear localization (nls2)' region; an α-helix; the brct 1 domain

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-asp1966val (accessed [today's date]).

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