Is DAG1 p.Arg76Cys (c.226C>T) pathogenic?

DAG1 p.Arg76Cys (c.226C>T) is classified Uncertain significance in DAG1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-08-07). AlphaMissense: likely benign (0.2446); Very rare (popmax 0.00891%, eas).

How common is DAG1 p.Arg76Cys (c.226C>T) in the general population?

DAG1 p.Arg76Cys (c.226C>T) is very rare (popmax 0.00891%, eas) (gnomAD).

What do computational predictors say about DAG1 p.Arg76Cys (c.226C>T)?

AlphaMissense predicts likely benign (score 0.2446) — an in-silico prediction, not a clinical call.

DAG1 p.Arg76Cys

c.226C>T · rs772814756 · VCV2440697

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2446 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00891%, eas)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2446	likely benign
REVEL	0.737	pathogenic-leaning
SaProt	LLR -9.90	tolerated
⇒ REVEL calls this damaging; AlphaMissense and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 1.7, phastCons 1
Regional constraint	o/e 0.82	unconstrained · MANE · 21 kb · p 0.0053 · regional, not allelic
Overall
CADD	28.8	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00891% East Asian · 4/44,878 alleles

Filtering AF 0.00298% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0018%

Overall 0.00142% 23/1,614,156 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00891%	11,220
African / African-American	0.00266%	37,524
Admixed American	0.00167%	60,024
Remaining individualsnot grpmax-eligible	0.0016%	62,510
European (non-Finnish)	0.00127%	78,668

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.Arg76Cys
Coding: c.226C>T
MANE Select: NM_004393
dbSNP: rs772814756
Type: single nucleotide variant
Location: chr3:49510760 (GRCh38)
Gene constraint: LOEUF 0.298 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 68.44 · 8 PDB
Residue 76: the 'required for laminin recognition' region

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

Similar variants

DAG1 p.Arg76His 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-arg76cys (accessed [today's date]).

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