Is DNMT3B p.Asp471= (c.1413C>T) pathogenic?

DNMT3B p.Asp471= (c.1413C>T) is classified Benign in DNMT3B (ClinVar, Multiple submitters, 3 submitters; last evaluated 2026-02-02). Low-frequency (popmax 4.26%, afr); Associated with immunodeficiency-centromeric instability-facial anomalies syndrome 1.

What condition is associated with DNMT3B p.Asp471= (c.1413C>T)?

DNMT3B p.Asp471= (c.1413C>T) is associated with immunodeficiency-centromeric instability-facial anomalies syndrome 1, immunodeficiency-centromeric instability-facial anomalies syndrome (ClinVar).

How common is DNMT3B p.Asp471= (c.1413C>T) in the general population?

DNMT3B p.Asp471= (c.1413C>T) is low-frequency (popmax 4.26%, afr) (gnomAD).

DNMT3B p.Asp471=

c.1413C>T · rs6119965 · VCV338168

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

low-frequency (popmax 4.26%, afr)

Conditions

immunodeficiency-centromeric instability-facial anomalies syndrome 1

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 -11	GERP -4.2
Overall
CADD	2.329	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 4.26% African / African-American · 3,195/75,062 alleles

Filtering AF 4.13% ClinGen BA1/BS1 input FAF95, joint · FAF99 4.08%

Overall 0.226% 3,645/1,614,150 alleles · low-frequency exomes 1,861/1,461,792 · genomes 1,784/152,358 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	4.26%	23
Admixed American	0.267%	375
Remaining individualsnot grpmax-eligible	0.261%	383
Middle Eastern	0.214%	466
South Asian	0.0154%	6,506
European (non-Finnish)	0.00822%	12,165
East Asian	0.00668%	14,960

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.Asp471=
Coding: c.1413C>T
MANE Select: NM_006892
dbSNP: rs6119965
Type: single nucleotide variant
Location: chr20:32797222 (GRCh38)
Gene constraint: LOEUF 0.396 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 73.18 · 47 PDB
Residue 471: the add domain; the 'interaction with the prc2/eed-ezh2 complex' region

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

Disease context

immunodeficiency-centromeric instability-facial anomalies syndrome 1 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: immunodeficiency-centromeric instability-facial anomalies syndrome

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-asp471 (accessed [today's date]).

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