Is DNMT3A p.Ala45fs (c.130_131dup) pathogenic?

DNMT3A p.Ala45fs (c.130131dup) is classified Likely pathogenic in DNMT3A (ClinVar, Single submitter, 1 submitter; last evaluated 2016-05-19). No gnomAD frequency available for this variant.

How common is DNMT3A p.Ala45fs (c.130_131dup) in the general population?

DNMT3A p.Ala45fs (c.130_131dup) is no gnomAD frequency available for this variant (gnomAD).

DNMT3A p.Ala45fs

c.130_131dup · rs1553427894 · VCV421277

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

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 3 of 23
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -3.9	GERP -3.1

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

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. 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.Ala45fs
Coding: c.130_131dup
MANE Select: NM_022552
dbSNP: rs1553427894
Type: Duplication
Location: chr2:25300184 (GRCh38)
Gene constraint: LOEUF 1.998 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 73.97 · 47 PDB
Residue 45: the 'disordered' region

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

Similar variants

DNMT3A p.Ala571fs Pathogenic/Likely pathogenic ★★ same type
DNMT3A p.Val60fs Pathogenic ★★ same type
DNMT3A p.Ala114fs Pathogenic ★ same type
DNMT3A p.Arg659fs Likely pathogenic ★ same type
DNMT3A p.Arg771fs Pathogenic ★ same type
DNMT3A p.Gln485fs Likely pathogenic ★ same type
DNMT3A p.Glu733Ter Pathogenic ★ same type
DNMT3A p.Gly10fs 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-ala45fs (accessed [today's date]).

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