Is DAGLB p.Leu451= (c.1351C>T) pathogenic?

DAGLB p.Leu451= (c.1351C>T) is classified Benign in DAGLB (ClinVar, Single submitter, 1 submitter; last evaluated 2018-04-10). Low-frequency (popmax 3.67%, afr).

How common is DAGLB p.Leu451= (c.1351C>T) in the general population?

DAGLB p.Leu451= (c.1351C>T) is low-frequency (popmax 3.67%, afr) (gnomAD).

DAGLB p.Leu451=

c.1351C>T · rs116541573 · VCV773888

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

low-frequency (popmax 3.67%, afr)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2	GERP 3.7, phastCons 0.98
Overall
CADD	3.143	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 3.67% African / African-American · 2,754/75,038 alleles

Filtering AF 3.56% ClinGen BA1/BS1 input FAF95, joint · FAF99 3.51%

Overall 0.197% 3,177/1,613,622 alleles · low-frequency

Ancestry group	Frequency	1 in
African / African-Americangrpmax	3.67%	27
Remaining individualsnot grpmax-eligible	0.286%	349
Admixed American	0.265%	377
Middle Eastern	0.132%	758
South Asian	0.0154%	6,503
European (non-Finnish)	0.00534%	18,726

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.Leu451=
Coding: c.1351C>T
MANE Select: NM_139179
dbSNP: rs116541573
Type: single nucleotide variant
Location: chr7:6416703 (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-leu451 (accessed [today's date]).

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