Is DAGLA p.Leu485Pro (c.1454T>C) pathogenic?

DAGLA p.Leu485Pro (c.1454T>C) is classified Uncertain significance in DAGLA (ClinVar, Single submitter, 1 submitter; last evaluated 2024-06-03). AlphaMissense: likely pathogenic (0.9999); Absent from gnomAD v4.1.

How common is DAGLA p.Leu485Pro (c.1454T>C) in the general population?

DAGLA p.Leu485Pro (c.1454T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about DAGLA p.Leu485Pro (c.1454T>C)?

AlphaMissense predicts likely pathogenic (score 0.9999) — an in-silico prediction, not a clinical call.

DAGLA p.Leu485Pro

c.1454T>C · VCV3384525

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9999 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9999	likely pathogenic · top 3% in DAGLA
REVEL	0.748	pathogenic-leaning
SaProt	LLR -19.01	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · T>A here scores Δ0.61 · evaluated, not missing
Constraint at this position
Conservation	phyloP 7.8	GERP 1.4, phastCons 1
Regional constraint	o/e 0.47	unconstrained · MANE · 6,332 bp · p 1.9e-29 · regional, not allelic
Overall
CADD	33.0	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.Leu485Pro
Coding: c.1454T>C
MANE Select: NM_006133
Type: single nucleotide variant
Location: chr11:61737264 (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

Similar variants

DAGLA p.Ile823Thr Uncertain significance ★★ ⚠ same type
DAGLA p.Ala767= Benign ★★ same type
DAGLA p.Gly735Val Benign ★★ same type
DAGLA p.Leu988Val Benign ★★ same type
DAGLA p.Phe157= Benign ★★ same type
DAGLA p.Phe335= Benign ★★ same type
DAGLA p.Val117Ile Likely benign ★★ same type
DAGLA p.Gln851Ter Likely pathogenic ★ 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/dagla-p-leu485pro (accessed [today's date]).

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