Is DAG1 p.Pro488Ser (c.1462C>T) pathogenic?

DAG1 p.Pro488Ser (c.1462C>T) is classified Uncertain significance in DAG1 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-05-25). AlphaMissense: likely benign (0.0692); Very rare (popmax 0.000339%, nfe).

How common is DAG1 p.Pro488Ser (c.1462C>T) in the general population?

DAG1 p.Pro488Ser (c.1462C>T) is very rare (popmax 0.000339%, nfe) (gnomAD).

What do computational predictors say about DAG1 p.Pro488Ser (c.1462C>T)?

AlphaMissense predicts likely benign (score 0.0692) — an in-silico prediction, not a clinical call.

DAG1 p.Pro488Ser

c.1462C>T · rs755443084 · VCV2440701

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0692 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000339%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0692	likely benign
REVEL	0.125	moderately benign-leaning
SaProt	LLR -6.99	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 1.2	GERP -0.03, phastCons 0.79
Regional constraint	o/e 0.88	unconstrained · MANE · 1,883 bp · p 0.0007 · regional, not allelic
Overall
CADD	14.26	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 0.000339% European (non-Finnish) · 4/1,180,042 alleles

Filtering AF 7.9e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 5.4e-05%

Overall 0.000248% 4/1,614,088 alleles · very rare exomes 3/1,461,888 · genomes 1/152,200 · joint denominator

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.Pro488Ser
Coding: c.1462C>T
MANE Select: NM_004393
dbSNP: rs755443084
Type: single nucleotide variant
Location: chr3:49531973 (GRCh38)
Gene constraint: LOEUF 0.298 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 68.44 · 8 PDB
Residue 488: the 'disordered' region

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

Similar variants

DAG1 p.Pro488Ala 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-pro488ser (accessed [today's date]).

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