Is DAG1 p.Thr421fs (c.1257del) pathogenic?

DAG1 p.Thr421fs (c.1257del) is classified Likely pathogenic in DAG1 (ClinVar, Single submitter, 1 submitter; last evaluated 2016-09-22). Absent from gnomAD.

How common is DAG1 p.Thr421fs (c.1257del) in the general population?

DAG1 p.Thr421fs (c.1257del) is absent from gnomAD (gnomAD).

DAG1 p.Thr421fs

c.1257del · rs886044452 · VCV290435

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 LoF-intolerant gene
NMD	escapes	premature termination codon in the last exon (3 of 3) — the truncated protein is likely expressed. PVS1 input, not an applied code
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 7.7	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: DAG1
Protein: p.Thr421fs
Coding: c.1257del
MANE Select: NM_004393
dbSNP: rs886044452
Type: Deletion
Location: chr3:49531768 (GRCh38)
Gene constraint: LOEUF 0.298 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 68.44 · 8 PDB
Residue 421: the 'disordered' region; the 'mucin-like domain' region

Full DAG1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DAG1 p.Thr531del Uncertain significance ★★ same type
DAG1 c.286-10del Benign/Likely benign ★★ same type
DAG1 p.Gln147fs Pathogenic ★ same type
DAG1 p.Gln206fs Pathogenic ★ same type
DAG1 p.Leu104fs Likely pathogenic ★ same type
DAG1 p.Leu306fs Pathogenic ★ same type
DAG1 p.Phe152fs Likely pathogenic ★ same type
DAG1 p.Phe241fs 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/dag1-p-thr421fs (accessed [today's date]).

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