Is DAGLB p.Leu403Pro (c.1208T>C) pathogenic?

DAGLB p.Leu403Pro (c.1208T>C) is classified Uncertain significance in DAGLB (ClinVar, Single submitter, 1 submitter; last evaluated 2024-03-15). AlphaMissense: likely benign (0.2271); Very rare (popmax 0.00334%, amr).

How common is DAGLB p.Leu403Pro (c.1208T>C) in the general population?

DAGLB p.Leu403Pro (c.1208T>C) is very rare (popmax 0.00334%, amr) (gnomAD).

What do computational predictors say about DAGLB p.Leu403Pro (c.1208T>C)?

AlphaMissense predicts likely benign (score 0.2271) — an in-silico prediction, not a clinical call.

DAGLB p.Leu403Pro

c.1208T>C · VCV3270836

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2271 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00334%, amr)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2271	likely benign
REVEL	0.184	benign-leaning
SaProt	LLR -10.37	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.13	GERP 1.5
Regional constraint	o/e 1.20	unconstrained · MANE · 38 kb · p 1.4e-09 · regional, not allelic
Overall
CADD	14.82	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 0.00334% Admixed American · 2/59,936 alleles

Filtering AF 0.00197% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00168%

Overall 0.00211% 34/1,610,720 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00334%	29,968
European (non-Finnish)	0.00272%	36,803

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.Leu403Pro
Coding: c.1208T>C
MANE Select: NM_139179
Type: single nucleotide variant
Location: chr7:6421737 (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-leu403pro (accessed [today's date]).

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