Is DNMT3A p.Val684fs (c.2051_2055del) pathogenic?

DNMT3A p.Val684fs (c.20512055del) is classified Likely pathogenic in DNMT3A (ClinVar, Single submitter, 1 submitter; last evaluated 2022-06-09). Absent from gnomAD.

How common is DNMT3A p.Val684fs (c.2051_2055del) in the general population?

DNMT3A p.Val684fs (c.2051_2055del) is absent from gnomAD (gnomAD).

DNMT3A p.Val684fs

c.2051_2055del · rs2465418029 · VCV2439901

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 17 of 23
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 6	GERP 1.9, phastCons 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.Val684fs
Coding: c.2051_2055del
MANE Select: NM_022552
dbSNP: rs2465418029
Type: Deletion
Location: chr2:25241589 (GRCh38)
Gene constraint: LOEUF 1.998 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 73.97 · 47 PDB
Residue 684: the sam-dependent mtase c5-type domain

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

Similar variants

DNMT3A c.1123del Pathogenic ★ same type
DNMT3A p.Ala246fs Pathogenic ★ same type
DNMT3A p.Ala449fs Pathogenic ★ same type
DNMT3A p.Arg598fs Pathogenic ★ same type
DNMT3A p.Arg891fs Pathogenic ★ same type
DNMT3A p.Asp11fs Pathogenic ★ same type
DNMT3A p.Asp394fs Pathogenic ★ same type
DNMT3A p.Asp81fs 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-val684fs (accessed [today's date]).

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