Is DNMT3B p.Ser32fs (c.93del) pathogenic?

DNMT3B p.Ser32fs (c.93del) is classified Pathogenic in DNMT3B (ClinVar, Single submitter, 1 submitter; last evaluated 2024-10-21). Associated with immunodeficiency-centromeric instability-facial anomalies syndrome.

What condition is associated with DNMT3B p.Ser32fs (c.93del)?

DNMT3B p.Ser32fs (c.93del) is associated with immunodeficiency-centromeric instability-facial anomalies syndrome (ClinVar).

DNMT3B p.Ser32fs

c.93del · VCV3664006

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

Conditions

immunodeficiency-centromeric instability-facial anomalies syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function in a LoF-intolerant gene
NMD	predicted	premature termination codon in exon 2 of 23
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 4.1	GERP 0.71, phastCons 1

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Variant & gene context

Gene: DNMT3B
Protein: p.Ser32fs
Coding: c.93del
MANE Select: NM_006892
Type: Deletion
Location: chr20:32780415 (GRCh38)
Gene constraint: LOEUF 0.396 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 73.18 · 47 PDB
Residue 32: the 'interaction with dnmt1 and dnmt3a' region; the 'disordered' region

Full DNMT3B gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

immunodeficiency-centromeric instability-facial anomalies syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

DNMT3B p.Ser32= Likely benign ★ same residue
DNMT3B p.Gln783fs Pathogenic/Likely pathogenic ★★ same condition
DNMT3B c.433-29_433-1del Likely pathogenic ★ same condition
DNMT3B p.Gly3fs Pathogenic ★ same condition
DNMT3B p.Leu489fs Pathogenic ★ same condition
DNMT3B p.Met332fs Pathogenic ★ same condition
DNMT3B p.Ser682fs Pathogenic ★ same condition
DNMT3B c.1067-20_1067-17del Likely benign ★ 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/dnmt3b-p-ser32fs (accessed [today's date]).

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