Is DAG1 p.Ile376Val (c.1126A>G) pathogenic?

DAG1 p.Ile376Val (c.1126A>G) is classified Uncertain significance in DAG1 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-06-10). AlphaMissense: likely benign (0.0785); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with DAG1 p.Ile376Val (c.1126A>G)?

DAG1 p.Ile376Val (c.1126A>G) is associated with Inborn genetic diseases (ClinVar).

How common is DAG1 p.Ile376Val (c.1126A>G) in the general population?

DAG1 p.Ile376Val (c.1126A>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about DAG1 p.Ile376Val (c.1126A>G)?

AlphaMissense predicts likely benign (score 0.0785) — an in-silico prediction, not a clinical call.

DAG1 p.Ile376Val

c.1126A>G · rs2472618723 · VCV2222881

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0785 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0785	likely benign
REVEL	0.074	moderately benign-leaning
SaProt	LLR -5.57	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 1.9, phastCons 1
Regional constraint	o/e 0.88	unconstrained · MANE · 1,883 bp · p 0.0007 · regional, not allelic
Overall
CADD	19.1	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

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: DAG1
Protein: p.Ile376Val
Coding: c.1126A>G
MANE Select: NM_004393
dbSNP: rs2472618723
Type: single nucleotide variant
Location: chr3:49531637 (GRCh38)
Gene constraint: LOEUF 0.298 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 68.44 · 8 PDB
Residue 376: the 'required for laminin recognition' region; the 'mucin-like domain' region

Full DAG1 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

Similar variants

DAG1 p.Ala279Ser Uncertain significance ★★ ⚠ same condition
DAG1 p.Ala285Val Uncertain significance ★★ ⚠ same condition
DAG1 p.Ala610Val Uncertain significance ★★ ⚠ same condition
DAG1 p.Ala695Thr Uncertain significance ★★ ⚠ same condition
DAG1 p.Ala789Val Uncertain significance ★★ ⚠ same condition
DAG1 p.Ala871Val Uncertain significance ★★ ⚠ same condition
DAG1 p.Arg311Pro Uncertain significance ★★ ⚠ same condition
DAG1 p.Arg402His Uncertain significance ★★ ⚠ 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/dag1-p-ile376val (accessed [today's date]).

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