Is DNMT3A p.Gln485fs (c.1450_1451dup) pathogenic?

DNMT3A p.Gln485fs (c.14501451dup) is classified Likely pathogenic in DNMT3A (ClinVar, Single submitter, 1 submitter; last evaluated 2017-05-05). Absent from gnomAD v4.1.

How common is DNMT3A p.Gln485fs (c.1450_1451dup) in the general population?

DNMT3A p.Gln485fs (c.1450_1451dup) is absent from gnomAD v4.1 (gnomAD).

DNMT3A p.Gln485fs

c.1450_1451dup · rs1131691760 · VCV430057

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,614,108)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function in a haploinsufficient gene (ClinGen)
NMD	predicted	premature termination codon in exon 12 of 23
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 0.63	GERP 0.47, phastCons 1

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

No allele count reported in gnomAD v4.1 (AN 1,614,108). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: DNMT3A
Protein: p.Gln485fs
Coding: c.1450_1451dup
MANE Select: NM_022552
dbSNP: rs1131691760
Type: Duplication
Location: chr2:25246042 (GRCh38)
Gene constraint: LOEUF 1.998 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 73.97 · 47 PDB
Residue 485: the add domain

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

Similar variants

DNMT3A p.Gln485Ter Likely pathogenic ★ same residue
DNMT3A p.Gln485Lys Uncertain significance ★ ⚠ same residue
DNMT3A p.Gln485Pro Uncertain significance ★ ⚠ same residue
DNMT3A p.Ala571fs Pathogenic/Likely pathogenic ★★ same type
DNMT3A p.Val60fs Pathogenic ★★ same type
DNMT3A p.Ala114fs Pathogenic ★ same type
DNMT3A p.Ala45fs Likely pathogenic ★ same type
DNMT3A p.Arg659fs Likely pathogenic ★ 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-gln485fs (accessed [today's date]).

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