Is DGKZ p.Pro752= (c.2256T>A) pathogenic?

DGKZ p.Pro752= (c.2256T>A) is classified Likely benign in DGKZ (ClinVar, Single submitter, 1 submitter; last evaluated 2022-07-06). Very rare (popmax 0.00223%, eas).

How common is DGKZ p.Pro752= (c.2256T>A) in the general population?

DGKZ p.Pro752= (c.2256T>A) is very rare (popmax 0.00223%, eas) (gnomAD).

DGKZ p.Pro752=

c.2256T>A · rs781361412 · VCV1396018

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00223%, eas)

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 -6	GERP -3
Overall
CADD	0.175	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00223% East Asian · 1/44,864 alleles

Overall 6.2e-05% 1/1,613,314 alleles · very rare exomes 1/1,461,160 · genomes 0/152,154 · joint denominator

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: DGKZ
Protein: p.Pro752=
Coding: c.2256T>A
MANE Select: NM_001199267
dbSNP: rs781361412
Type: single nucleotide variant
Location: chr11:46377129 (GRCh38)
Gene constraint: LOEUF 0.451 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 77.94 · 1 PDB

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

Similar variants

DGKZ p.Pro752Ala Uncertain significance ★ ⚠ same residue
DGKZ c.162-1007C>T Uncertain significance ★★ same type
DGKZ c.162-335G>A Uncertain significance ★★ same type
DGKZ c.162-350C>T Uncertain significance ★★ same type
DGKZ c.162-364G>A Uncertain significance ★★ same type
DGKZ c.162-461C>T Uncertain significance ★★ same type
DGKZ c.162-491G>A Uncertain significance ★★ same type
DGKZ c.162-517A>T 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/dgkz-p-pro752 (accessed [today's date]).

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