Is DAGLA p.Asp456Val (c.1367A>T) pathogenic?

DAGLA p.Asp456Val (c.1367A>T) is classified Uncertain significance in DAGLA (ClinVar, Single submitter, 1 submitter; last evaluated 2025-06-24). AlphaMissense: likely pathogenic (0.9373); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with DAGLA p.Asp456Val (c.1367A>T)?

DAGLA p.Asp456Val (c.1367A>T) is associated with Inborn genetic diseases (ClinVar).

How common is DAGLA p.Asp456Val (c.1367A>T) in the general population?

DAGLA p.Asp456Val (c.1367A>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about DAGLA p.Asp456Val (c.1367A>T)?

AlphaMissense predicts likely pathogenic (score 0.9373) — an in-silico prediction, not a clinical call.

DAGLA p.Asp456Val

c.1367A>T · VCV4237492

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9373 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.9373	likely pathogenic
REVEL	0.445	indeterminate
SaProt	LLR -10.24	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 1.5, phastCons 1
Regional constraint	o/e 0.47	unconstrained · MANE · 6,332 bp · p 1.9e-29 · regional, not allelic
Overall
CADD	28.0	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: DAGLA
Protein: p.Asp456Val
Coding: c.1367A>T
MANE Select: NM_006133
Type: single nucleotide variant
Location: chr11:61736346 (GRCh38)
Gene constraint: LOEUF 0.305 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 63.87

Full DAGLA 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

DAGLA p.Ile823Thr Uncertain significance ★★ ⚠ same condition
DAGLA p.Val117Ile Likely benign ★★ same condition
DAGLA p.Ala253Thr Uncertain significance ★ ⚠ same condition
DAGLA p.Ala336Thr Uncertain significance ★ ⚠ same condition
DAGLA p.Ala351Thr Uncertain significance ★ ⚠ same condition
DAGLA p.Ala518Ser Uncertain significance ★ ⚠ same condition
DAGLA p.Ala614Ser Uncertain significance ★ ⚠ same condition
DAGLA p.Ala716Val 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/dagla-p-asp456val (accessed [today's date]).

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