Is DAGLB p.Gly331Asp (c.992G>A) pathogenic?

DAGLB p.Gly331Asp (c.992G>A) is classified Uncertain significance in DAGLB (ClinVar, Single submitter, 1 submitter; last evaluated 2025-03-22). AlphaMissense: likely benign (0.2892); Ultra-rare (popmax 0.024%, afr).

How common is DAGLB p.Gly331Asp (c.992G>A) in the general population?

DAGLB p.Gly331Asp (c.992G>A) is ultra-rare (popmax 0.024%, afr) (gnomAD).

What do computational predictors say about DAGLB p.Gly331Asp (c.992G>A)?

AlphaMissense predicts likely benign (score 0.2892) — an in-silico prediction, not a clinical call.

DAGLB p.Gly331Asp

c.992G>A · VCV4009325

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2892 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.024%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2892	likely benign
REVEL	0.152	moderately benign-leaning
SaProt	LLR -6.70	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 5.3	GERP 1.9, phastCons 1
Regional constraint	o/e 1.20	unconstrained · MANE · 38 kb · p 1.4e-09 · regional, not allelic
Overall
CADD	22.4	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 0.024% African / African-American · 18/75,048 alleles

Filtering AF 0.0154% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0128%

Overall 0.00112% 18/1,614,054 alleles · ultra-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: DAGLB
Protein: p.Gly331Asp
Coding: c.992G>A
MANE Select: NM_139179
Type: single nucleotide variant
Location: chr7:6426052 (GRCh38)
Gene constraint: LOEUF 1.121 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 73.18

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

Similar variants

DAGLB p.Gly331Ser Uncertain significance ★ ⚠ same residue
DAGLB p.Asp247Glu Uncertain significance ★★ ⚠ same type
DAGLB p.Asn131= Benign/Likely benign ★★ same type
DAGLB p.Gly632= Benign/Likely benign ★★ same type
DAGLB p.Ala116Thr Uncertain significance ★ ⚠ same type
DAGLB p.Ala12Thr Uncertain significance ★ ⚠ same type
DAGLB p.Ala145Thr Uncertain significance ★ ⚠ same type
DAGLB p.Ala145Val 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/daglb-p-gly331asp (accessed [today's date]).

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