Is DNMT3A p.Tyr481Ter (c.1443C>A) pathogenic?

DNMT3A p.Tyr481Ter (c.1443C>A) is classified Likely pathogenic in DNMT3A (ClinVar, Single submitter, 1 submitter; last evaluated 2019-12-01). Absent from gnomAD v4.1.

How common is DNMT3A p.Tyr481Ter (c.1443C>A) in the general population?

DNMT3A p.Tyr481Ter (c.1443C>A) is absent from gnomAD v4.1 (gnomAD).

DNMT3A p.Tyr481Ter

c.1443C>A · rs145465364 · VCV872726

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,614,116)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function in a haploinsufficient gene (ClinGen)
NMD	predicted	premature termination codon in exon 12 of 23
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -1.2	GERP -3
Overall
CADD	33.0	PHRED · no single calibrated threshold — expert panels disagree

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 1,614,116). 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.Tyr481Ter
Coding: c.1443C>A
MANE Select: NM_022552
dbSNP: rs145465364
Type: single nucleotide variant
Location: chr2:25246051 (GRCh38)
Gene constraint: LOEUF 1.998 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 73.97 · 47 PDB
Residue 481: an α-helix

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

Similar variants

DNMT3A p.Tyr481= Benign/Likely benign ★★ same residue
DNMT3A c.1667+1G>A Likely pathogenic ★★ same type
DNMT3A c.1937-2A>G Pathogenic ★★ same type
DNMT3A c.2478+1G>A Pathogenic/Likely pathogenic ★★ same type
DNMT3A c.2479-1G>A Likely pathogenic ★★ same type
DNMT3A p.Arg143Ter Pathogenic ★★ same type
DNMT3A p.Arg301Trp Pathogenic/Likely pathogenic ★★ same type
DNMT3A p.Arg320Ter Pathogenic/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-tyr481ter (accessed [today's date]).

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