Is DNMT3A p.Asn360del (c.1077CAA[1]) pathogenic?

DNMT3A p.Asn360del (c.1077CAA[1]) is classified Uncertain significance in DNMT3A (ClinVar, Single submitter, 1 submitter; last evaluated 2021-11-10). Very rare (popmax 8.47e-05%, nfe).

How common is DNMT3A p.Asn360del (c.1077CAA[1]) in the general population?

DNMT3A p.Asn360del (c.1077CAA[1]) is very rare (popmax 8.47e-05%, nfe) (gnomAD).

DNMT3A p.Asn360del

c.1077CAA[1] · rs2465546867 · VCV2440978

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 8.47e-05%, nfe)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 3.3	GERP 0.34, phastCons 1

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.47e-05% European (non-Finnish) · 1/1,180,010 alleles

Overall 6.84e-05% 1/1,461,838 alleles · very rare

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: DNMT3A
Protein: p.Asn360del
Coding: c.1077CAA[1]
MANE Select: NM_022552
dbSNP: rs2465546867
Type: Microsatellite
Location: chr2:25247091 (GRCh38)
Gene constraint: LOEUF 1.998 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 73.97 · 47 PDB
Residue 360: the 'interaction with dnmt1 and dnmt3b' region; an α-helix

Full DNMT3A gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DNMT3A p.Asn360= Likely benign ★ same residue
DNMT3A p.Phe732del Uncertain significance ★★ same type
DNMT3A p.Ile780fs Likely pathogenic ★ same type
DNMT3A p.Phe752del Likely pathogenic ★ same type
DNMT3A p.Asp531del Uncertain significance ★ same type
DNMT3A p.Ter913ArgextTer? Uncertain significance ★ same type
DNMT3A c.1851+2_1851+3del Uncertain significance same type
DNMT3A c.2174-4_2174-3del Likely benign same type

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/dnmt3a-p-asn360del (accessed [today's date]).

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