Is DAG1 p.Ser52Pro (c.154T>C) pathogenic?

DAG1 p.Ser52Pro (c.154T>C) is classified Uncertain significance in DAG1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-20). AlphaMissense: likely pathogenic (0.6352); Very rare (popmax 8.47e-05%, nfe); Associated with Inborn genetic diseases.

What condition is associated with DAG1 p.Ser52Pro (c.154T>C)?

DAG1 p.Ser52Pro (c.154T>C) is associated with Inborn genetic diseases (ClinVar).

How common is DAG1 p.Ser52Pro (c.154T>C) in the general population?

DAG1 p.Ser52Pro (c.154T>C) is very rare (popmax 8.47e-05%, nfe) (gnomAD).

What do computational predictors say about DAG1 p.Ser52Pro (c.154T>C)?

AlphaMissense predicts likely pathogenic (score 0.6352) — an in-silico prediction, not a clinical call.

DAG1 p.Ser52Pro

c.154T>C · rs2472166182 · VCV3079993

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6352 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.47e-05%, nfe)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.6352	likely pathogenic
REVEL	0.375	indeterminate
SaProt	LLR -6.83	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 7.9	GERP 1.7, phastCons 1
Regional constraint	o/e 0.82	unconstrained · MANE · 21 kb · p 0.0053 · regional, not allelic
Overall
CADD	26.4	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 8.47e-05% European (non-Finnish) · 1/1,180,020 alleles

Overall 6.84e-05% 1/1,461,892 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.Ser52Pro
Coding: c.154T>C
MANE Select: NM_004393
dbSNP: rs2472166182
Type: single nucleotide variant
Location: chr3:49510688 (GRCh38)
Gene constraint: LOEUF 0.298 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 68.44 · 8 PDB
Residue 52: the 'required for laminin recognition' 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-ser52pro (accessed [today's date]).

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