Is DNMT3A p.Gln415= (c.1245G>A) pathogenic?

DNMT3A p.Gln415= (c.1245G>A) is classified Likely benign in DNMT3A (ClinVar, Single submitter, 1 submitter; last evaluated 2025-03-10). Absent from gnomAD v4.1; Associated with Tatton-Brown-Rahman overgrowth syndrome.

What condition is associated with DNMT3A p.Gln415= (c.1245G>A)?

DNMT3A p.Gln415= (c.1245G>A) is associated with Tatton-Brown-Rahman overgrowth syndrome (ClinVar).

How common is DNMT3A p.Gln415= (c.1245G>A) in the general population?

DNMT3A p.Gln415= (c.1245G>A) is absent from gnomAD v4.1 (gnomAD).

DNMT3A p.Gln415=

c.1245G>A · rs2149302502 · VCV2866217

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

Tatton-Brown-Rahman overgrowth syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.7	GERP 1.7, phastCons 1
Overall
CADD	12.87	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: DNMT3A
Protein: p.Gln415=
Coding: c.1245G>A
MANE Select: NM_022552
dbSNP: rs2149302502
Type: single nucleotide variant
Location: chr2:25246654 (GRCh38)
Gene constraint: LOEUF 1.998 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 73.97 · 47 PDB
Residue 415: a turn

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

Disease context

Tatton-Brown-Rahman overgrowth syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

DNMT3A p.Gln415Ter Pathogenic ★ same residue
DNMT3A p.Gln415fs Pathogenic ★ same residue
DNMT3A p.Gln415Leu Uncertain significance ★ ⚠ same residue
DNMT3A c.1667+1G>A Likely pathogenic ★★ same condition
DNMT3A c.1937-2A>G Pathogenic ★★ same condition
DNMT3A c.2478+1G>A Pathogenic/Likely pathogenic ★★ same condition
DNMT3A c.2479-1G>A Likely pathogenic ★★ same condition
DNMT3A p.Arg143Ter 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-gln415 (accessed [today's date]).

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