Is DAG1 p.Arg481Pro (c.1442G>C) pathogenic?

DAG1 p.Arg481Pro (c.1442G>C) is classified Uncertain significance in DAG1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2020-06-30). AlphaMissense: likely benign (0.2204); Very rare (popmax 0.000763%, nfe).

How common is DAG1 p.Arg481Pro (c.1442G>C) in the general population?

DAG1 p.Arg481Pro (c.1442G>C) is very rare (popmax 0.000763%, nfe) (gnomAD).

What do computational predictors say about DAG1 p.Arg481Pro (c.1442G>C)?

AlphaMissense predicts likely benign (score 0.2204) — an in-silico prediction, not a clinical call.

DAG1 p.Arg481Pro

c.1442G>C · rs1256677839 · VCV447234

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.2204 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000763%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2204	likely benign
REVEL	0.145	moderately benign-leaning
SaProt	LLR -4.03	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 8.6	GERP 0.85, phastCons 1
Regional constraint	o/e 0.88	unconstrained · MANE · 1,883 bp · p 0.0007 · regional, not allelic
Overall
CADD	21.4	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

Grpmax group 0.000763% European (non-Finnish) · 9/1,180,026 alleles

Filtering AF 0.000359% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00026%

Overall 0.000616% 9/1,461,886 alleles · very rare

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: DAG1
Protein: p.Arg481Pro
Coding: c.1442G>C
MANE Select: NM_004393
dbSNP: rs1256677839
Type: single nucleotide variant
Location: chr3:49531953 (GRCh38)
Gene constraint: LOEUF 0.298 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 68.44 · 8 PDB
Residue 481: the 'o-glycosylated at seven sites with galnac' region; 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.Arg481Cys Uncertain significance ★ ⚠ same residue
DAG1 p.Ser14Ter Pathogenic ★★ same type
DAG1 p.Trp110Ter Pathogenic/Likely pathogenic ★★ same type
DAG1 p.Ala135Ser Uncertain significance ★★ ⚠ same type
DAG1 p.Ala135Thr Uncertain significance ★★ ⚠ same type
DAG1 p.Ala279Ser Uncertain significance ★★ ⚠ same type
DAG1 p.Ala285Thr Uncertain significance ★★ ⚠ same type
DAG1 p.Ala285Val Uncertain significance ★★ ⚠ 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-arg481pro (accessed [today's date]).

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