Is DNMT3B p.Ser112= (c.336C>T) pathogenic?

DNMT3B p.Ser112= (c.336C>T) is classified Benign/Likely benign in DNMT3B (ClinVar, Multiple submitters, 4 submitters; last evaluated 2026-01-31). Rare (popmax 0.54%, sas); Associated with immunodeficiency-centromeric instability-facial anomalies syndrome.

What condition is associated with DNMT3B p.Ser112= (c.336C>T)?

DNMT3B p.Ser112= (c.336C>T) is associated with immunodeficiency-centromeric instability-facial anomalies syndrome, immunodeficiency-centromeric instability-facial anomalies syndrome 1 (ClinVar).

How common is DNMT3B p.Ser112= (c.336C>T) in the general population?

DNMT3B p.Ser112= (c.336C>T) is rare (popmax 0.54%, sas) (gnomAD).

DNMT3B p.Ser112=

c.336C>T · rs199763590 · VCV737007

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

rare (popmax 0.54%, sas)

Conditions

immunodeficiency-centromeric instability-facial anomalies syndrome

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 2.6	GERP 0.75, phastCons 1
Overall
CADD	12.2	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.54% South Asian · 492/91,088 alleles

Filtering AF 0.501% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.485%

Overall 0.0432% 698/1,614,056 alleles · rare exomes 658/1,461,676 · genomes 40/152,380 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.54%	185
Middle Eastern	0.132%	758
Remaining individualsnot grpmax-eligible	0.0816%	1,226
East Asian	0.0156%	6,413
Admixed American	0.0133%	7,505
European (non-Finnish)	0.011%	9,077
African / African-American	0.00266%	37,532

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: DNMT3B
Protein: p.Ser112=
Coding: c.336C>T
MANE Select: NM_006892
dbSNP: rs199763590
Type: single nucleotide variant
Location: chr20:32786531 (GRCh38)
Gene constraint: LOEUF 0.396 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 73.18 · 47 PDB
Residue 112: 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

Also linked: immunodeficiency-centromeric instability-facial anomalies syndrome 1

Similar variants

DNMT3B c.2421-11G>A Pathogenic/Likely pathogenic ★★ same condition
DNMT3B p.Ala603Thr Pathogenic/Likely pathogenic ★★ same condition
DNMT3B p.Arg826Cys Pathogenic/Likely pathogenic ★★ same condition
DNMT3B p.Arg840Gln Likely pathogenic ★★ same condition
DNMT3B p.Asp653Asn Pathogenic/Likely pathogenic ★★ same condition
DNMT3B p.His814Arg Likely pathogenic ★★ ⚠ same condition
DNMT3B p.Val613Ala Pathogenic/Likely pathogenic ★★ same condition
DNMT3B p.Val726Gly Pathogenic/Likely pathogenic ★★ 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-ser112 (accessed [today's date]).

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