Is DNMT3A p.Ser304del (c.911_913del) pathogenic?

DNMT3A p.Ser304del (c.911913del) is classified Conflicting classifications of pathogenicity in DNMT3A (ClinVar, Conflicting submitters, 5 submitters; last evaluated 2024-09-04). Absent from gnomAD; Associated with Inborn genetic diseases.

What condition is associated with DNMT3A p.Ser304del (c.911_913del)?

DNMT3A p.Ser304del (c.911_913del) is associated with Inborn genetic diseases, Tatton-Brown-Rahman overgrowth syndrome, Heyn-Sproul-Jackson syndrome (ClinVar).

How common is DNMT3A p.Ser304del (c.911_913del) in the general population?

DNMT3A p.Ser304del (c.911_913del) is absent from gnomAD (gnomAD).

DNMT3A p.Ser304del

c.911_913del · rs1674984864 · VCV916110

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 5 submitters

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

Inborn genetic diseases

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 7.7	GERP 1.9, phastCons 1

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.Ser304del
Coding: c.911_913del
MANE Select: NM_022552
dbSNP: rs1674984864
Type: Deletion
Location: chr2:25247692 (GRCh38)
Gene constraint: LOEUF 1.998 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 73.97 · 47 PDB
Residue 304: the pwwp domain; the 'interaction with dnmt1 and dnmt3b' region

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: Tatton-Brown-Rahman overgrowth syndrome Heyn-Sproul-Jackson syndrome

Similar variants

DNMT3A c.1123del Pathogenic ★ same condition
DNMT3A p.Ala246fs Pathogenic ★ same condition
DNMT3A p.Arg598fs Pathogenic ★ same condition
DNMT3A p.Arg891fs Pathogenic ★ same condition
DNMT3A p.Asp11fs Pathogenic ★ same condition
DNMT3A p.Asp394fs Pathogenic ★ same condition
DNMT3A p.Cys583fs Pathogenic ★ same condition
DNMT3A p.Gln415fs 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/dnmt3a-p-ser304del (accessed [today's date]).

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