Is DGKA p.Pro343= (c.1029G>A) pathogenic?

DGKA p.Pro343= (c.1029G>A) is classified Likely benign in DGKA (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-03-27). Very rare (popmax 0.0022%, sas); Associated with DGKA-related disorder.

What condition is associated with DGKA p.Pro343= (c.1029G>A)?

DGKA p.Pro343= (c.1029G>A) is associated with DGKA-related disorder (ClinVar).

How common is DGKA p.Pro343= (c.1029G>A) in the general population?

DGKA p.Pro343= (c.1029G>A) is very rare (popmax 0.0022%, sas) (gnomAD).

DGKA p.Pro343=

c.1029G>A · rs755791540 · VCV3057251

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.0022%, sas)

Conditions

DGKA-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 0.35	GERP -2.5, phastCons 0.95
Overall
CADD	4.37	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0022% South Asian · 2/91,062 alleles

Filtering AF 0.000878% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000717%

Overall 0.00155% 25/1,613,930 alleles · very rare

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0064%	15,621
South Asiangrpmax	0.0022%	45,531
Admixed American	0.00167%	59,980
European (non-Finnish)	0.00144%	69,411
African / African-American	0.00134%	74,900

Remaining individuals 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: DGKA
Protein: p.Pro343=
Coding: c.1029G>A
MANE Select: NM_001345
dbSNP: rs755791540
Type: single nucleotide variant
Location: chr12:55940908 (GRCh38)
Gene constraint: LOEUF 0.419 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 82.51 · 2 PDB

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

Disease context

DGKA-related disorder

Similar variants

DGKA p.Pro343Leu Uncertain significance ★ ⚠ same residue
DGKA p.Asp203= Benign same condition
DGKA p.Gln391= Benign same condition
DGKA p.Gln398= Benign same condition
DGKA p.Gly476= Benign same condition
DGKA p.Ile521Val Likely benign same condition
DGKA p.Lys137Arg Likely benign same condition
DGKA p.Phe559= 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/dgka-p-pro343 (accessed [today's date]).

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