Is DNMT3B p.Asp385= (c.1155C>T) pathogenic?

DNMT3B p.Asp385= (c.1155C>T) is classified Likely benign in DNMT3B (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-22). Ultra-rare (popmax 0.0134%, eas); Associated with immunodeficiency-centromeric instability-facial anomalies syndrome.

What condition is associated with DNMT3B p.Asp385= (c.1155C>T)?

DNMT3B p.Asp385= (c.1155C>T) is associated with immunodeficiency-centromeric instability-facial anomalies syndrome (ClinVar).

How common is DNMT3B p.Asp385= (c.1155C>T) in the general population?

DNMT3B p.Asp385= (c.1155C>T) is ultra-rare (popmax 0.0134%, eas) (gnomAD).

DNMT3B p.Asp385=

c.1155C>T · rs556733675 · VCV734567

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0134%, eas)

Conditions

immunodeficiency-centromeric instability-facial anomalies syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.104	moderately benign-leaning
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -20	GERP -3.6
Overall
CADD	0.206	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0134% East Asian · 6/44,894 alleles

Filtering AF 0.00579% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00394%

Overall 0.00322% 52/1,613,992 alleles · ultra-rare exomes 47/1,461,866 · genomes 5/152,126 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0134%	7,482
Admixed American	0.00667%	14,997
European (non-Finnish)	0.0033%	30,257
Remaining individualsnot grpmax-eligible	0.0016%	62,480
African / African-American	0.00134%	74,904
South Asian	0.0011%	91,074

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.Asp385=
Coding: c.1155C>T
MANE Select: NM_006892
dbSNP: rs556733675
Type: single nucleotide variant
Location: chr20:32795437 (GRCh38)
Gene constraint: LOEUF 0.396 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 73.18 · 47 PDB
Residue 385: 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.Asp385Glu Uncertain significance ★ ⚠ same residue
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

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-asp385 (accessed [today's date]).

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