Is DGKD p.Leu891= (c.2673A>G) pathogenic?

DGKD p.Leu891= (c.2673A>G) is classified Benign in DGKD (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-09-24). Common (popmax 12.5%, afr) — too common for a highly-penetrant pathogenic allele; Associated with DGKD-related disorder.

What condition is associated with DGKD p.Leu891= (c.2673A>G)?

DGKD p.Leu891= (c.2673A>G) is associated with DGKD-related disorder (ClinVar).

DGKD p.Leu891=

Q: How common is DGKD p.Leu891= (c.2673A>G) in the general population?

DGKD p.Leu891= (c.2673A>G) is common (popmax 12.5%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.2673A>G · rs61739478 · VCV3060583

Benign No assertion criteria

Classification

Benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Common

common (popmax 12.5%, afr) — too common for a highly-penetrant pathogenic allele

Conditions

DGKD-related disorder

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 5.1	GERP -1.8, phastCons 1
Overall
CADD	10.19	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 12.5% African / African-American · 9,404/74,986 alleles

Filtering AF 12.3% ClinGen BA1/BS1 input FAF95, joint · FAF99 12.2%

Overall 1.27% 20,407/1,610,358 alleles · common

Ancestry group	Frequency	1 in
African / African-Americangrpmax	12.5%	8
Admixed American	3.34%	30
East Asian	2.18%	46
Remaining individualsnot grpmax-eligible	1.83%	55
Ashkenazi Jewishnot grpmax-eligible	1.71%	58
Middle Eastern	0.994%	101
Finnishnot grpmax-eligible	0.979%	102
South Asian	0.779%	128
European (non-Finnish)	0.424%	236

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: DGKD
Protein: p.Leu891=
Coding: c.2673A>G
MANE Select: NM_152879
dbSNP: rs61739478
Type: single nucleotide variant
Location: chr2:233458376 (GRCh38)
Gene constraint: LOEUF 0.547 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 72.02 · 2 PDB

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

Disease context

DGKD-related disorder

Similar variants

DGKD p.Ala847= Likely benign same condition
DGKD p.Asn1034Ser Benign same condition
DGKD p.Glu971Lys Likely benign ⚠ same condition
DGKD p.Gly1099Cys Likely benign ⚠ same condition
DGKD p.Pro597= Likely benign same condition
DGKD p.Ser498= Benign same condition
DGKD p.Ser529= Likely benign same condition
DGKD p.Thr759= Likely benign same condition

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/dgkd-p-leu891 (accessed [today's date]).

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