Is DAG1 p.Ala757Val (c.2270C>T) pathogenic?

DAG1 p.Ala757Val (c.2270C>T) is classified Uncertain significance in DAG1 (ClinVar, Single submitter, 1 submitter; last evaluated 2017-05-08). AlphaMissense: likely pathogenic (0.9475); Very rare (popmax 6.84e-05%).

How common is DAG1 p.Ala757Val (c.2270C>T) in the general population?

DAG1 p.Ala757Val (c.2270C>T) is very rare (popmax 6.84e-05%) (gnomAD).

What do computational predictors say about DAG1 p.Ala757Val (c.2270C>T)?

AlphaMissense predicts likely pathogenic (score 0.9475) — an in-silico prediction, not a clinical call.

DAG1 p.Ala757Val

c.2270C>T · rs1131691522 · VCV429674

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9475 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 6.84e-05%)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.9475	likely pathogenic
REVEL	0.379	indeterminate
SaProt	LLR -5.92	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 1.9, phastCons 1
Regional constraint	o/e 0.88	unconstrained · MANE · 1,883 bp · p 0.0007 · regional, not allelic
Overall
CADD	26.5	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 6.84e-05%

Overall 6.84e-05% 1/1,461,756 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.Ala757Val
Coding: c.2270C>T
MANE Select: NM_004393
dbSNP: rs1131691522
Type: single nucleotide variant
Location: chr3:49532781 (GRCh38)
Gene constraint: LOEUF 0.298 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 68.44 · 8 PDB

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

Similar variants

DAG1 p.Ala757= Benign ★★ 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-ala757val (accessed [today's date]).

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