Is DNMT1 p.Lys660del (c.1978_1980del) pathogenic?

DNMT1 p.Lys660del (c.19781980del) is classified Uncertain significance in DNMT1 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-02-24). Absent from gnomAD; Associated with hereditary sensory neuropathy-deafness-dementia syndrome.

What condition is associated with DNMT1 p.Lys660del (c.1978_1980del)?

DNMT1 p.Lys660del (c.1978_1980del) is associated with hereditary sensory neuropathy-deafness-dementia syndrome (ClinVar).

How common is DNMT1 p.Lys660del (c.1978_1980del) in the general population?

DNMT1 p.Lys660del (c.1978_1980del) is absent from gnomAD (gnomAD).

DNMT1 p.Lys660del

Q: How is Hereditary sensory neuropathy-deafness-dementia syndrome inherited?

Typically Autosomal dominant (Orphanet). A genetic counselor can assess individual risk for a family.

c.1978_1980del · rs2145307223 · VCV1375593

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

hereditary sensory neuropathy-deafness-dementia syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 7.6	GERP 2.4, phastCons 1

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: DNMT1
Protein: p.Lys660del
Coding: c.1978_1980del
MANE Select: NM_001130823
dbSNP: rs2145307223
Type: Deletion
Location: chr19:10154332 (GRCh38)
Gene constraint: LOEUF 0.15 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 77.88 · 29 PDB
Residue 660: the 'required for activity' region

Full DNMT1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

hereditary sensory neuropathy-deafness-dementia syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Hereditary sensory neuropathy-deafness-dementia syndrome (Orphanet):

Inheritance: Autosomal dominant
Onset: Adolescent, Adult

Similar variants

DNMT1 c.1044-8del Benign/Likely benign ★★ same condition
DNMT1 c.1044-9_1044-8del Benign ★★ same condition
DNMT1 c.3116+14_3116+32del Likely benign ★★ same condition
DNMT1 c.1008+18_1008+34del Uncertain significance ★ same condition
DNMT1 c.446-7del Conflicting classifications of pathogenicity ★ same condition
DNMT1 p.Arg314del Uncertain significance ★ same condition
DNMT1 p.Asn408del Uncertain significance ★ same condition
DNMT1 p.Asp213del Uncertain significance ★ 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/dnmt1-p-lys660del (accessed [today's date]).

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