Is DAGLB p.Met63Val (c.187A>G) pathogenic?

DAGLB p.Met63Val (c.187A>G) is classified Uncertain significance in DAGLB (ClinVar, Single submitter, 1 submitter; last evaluated 2024-02-06). AlphaMissense: likely benign (0.0845); Very rare (popmax 0.00402%, afr).

How common is DAGLB p.Met63Val (c.187A>G) in the general population?

DAGLB p.Met63Val (c.187A>G) is very rare (popmax 0.00402%, afr) (gnomAD).

What do computational predictors say about DAGLB p.Met63Val (c.187A>G)?

AlphaMissense predicts likely benign (score 0.0845) — an in-silico prediction, not a clinical call.

DAGLB p.Met63Val

c.187A>G · rs756285755 · VCV3080021

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0845 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00402%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0845	likely benign
REVEL	0.064	moderately benign-leaning
SaProt	LLR -5.80	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 -0.03	GERP -3, phastCons 0.002
Regional constraint	o/e 1.20	unconstrained · MANE · 38 kb · p 1.4e-09 · regional, not allelic
Overall
CADD	9.258	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 0.00402% African / African-American · 3/74,714 alleles

Filtering AF 0.00107% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000496%

Overall 0.000558% 9/1,613,430 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00402%	24,905
European (non-Finnish)	0.000509%	196,654

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.Met63Val
Coding: c.187A>G
MANE Select: NM_139179
dbSNP: rs756285755
Type: single nucleotide variant
Location: chr7:6446013 (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.Met63Thr 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-met63val (accessed [today's date]).

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