Is DNMT3B p.Ala514= (c.1542C>A) pathogenic?

DNMT3B p.Ala514= (c.1542C>A) is classified Likely benign in DNMT3B (ClinVar, Single submitter, 1 submitter; last evaluated 2023-10-16). Absent from gnomAD v4.1; Associated with immunodeficiency-centromeric instability-facial anomalies syndrome.

What condition is associated with DNMT3B p.Ala514= (c.1542C>A)?

DNMT3B p.Ala514= (c.1542C>A) is associated with immunodeficiency-centromeric instability-facial anomalies syndrome (ClinVar).

How common is DNMT3B p.Ala514= (c.1542C>A) in the general population?

DNMT3B p.Ala514= (c.1542C>A) is absent from gnomAD v4.1 (gnomAD).

DNMT3B p.Ala514=

c.1542C>A · rs140714949 · VCV2768953

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

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 -9.7	GERP -4.1
Overall
CADD	0.109	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: DNMT3B
Protein: p.Ala514=
Coding: c.1542C>A
MANE Select: NM_006892
dbSNP: rs140714949
Type: single nucleotide variant
Location: chr20:32798511 (GRCh38)
Gene constraint: LOEUF 0.396 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 73.18 · 47 PDB
Residue 514: the add domain; the 'interaction with the prc2/eed-ezh2 complex' region; an α-helix

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 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-ala514 (accessed [today's date]).

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