Is DAGLB p.Ile596Thr (c.1787T>C) pathogenic?

DAGLB p.Ile596Thr (c.1787T>C) is classified Benign in DAGLB (ClinVar, Single submitter, 1 submitter; last evaluated 2019-12-31). AlphaMissense: likely pathogenic (0.88); Rare (popmax 0.909%, nfe).

How common is DAGLB p.Ile596Thr (c.1787T>C) in the general population?

DAGLB p.Ile596Thr (c.1787T>C) is rare (popmax 0.909%, nfe) (gnomAD).

What do computational predictors say about DAGLB p.Ile596Thr (c.1787T>C)?

AlphaMissense predicts likely pathogenic (score 0.88) — an in-silico prediction, not a clinical call.

DAGLB p.Ile596Thr

c.1787T>C · rs139753251 · VCV771156

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.88 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.909%, nfe)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.88	likely pathogenic
REVEL	0.476	indeterminate
SaProt	LLR -13.48	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 5.1, phastCons 1
Regional constraint	o/e 1.20	unconstrained · MANE · 38 kb · p 1.4e-09 · regional, not allelic
Overall
CADD	25.5	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.909% European (non-Finnish) · 10,553/1,160,484 alleles

Filtering AF 0.895% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.889%

Overall 0.805% 12,732/1,580,808 alleles · rare

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	1.64%	61
European (non-Finnish)grpmax	0.909%	110
Remaining individualsnot grpmax-eligible	0.782%	128
Admixed American	0.456%	219
Ashkenazi Jewishnot grpmax-eligible	0.439%	228
South Asian	0.199%	502
Middle Eastern	0.169%	593
African / African-American	0.146%	683
East Asian	0.00453%	22,072

Finnish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Ile596Thr
Coding: c.1787T>C
MANE Select: NM_139179
dbSNP: rs139753251
Type: single nucleotide variant
Location: chr7:6410163 (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.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
DAGLB p.Ala146Gly 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-ile596thr (accessed [today's date]).

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