Is DGKD p.Pro8= (c.24T>A) pathogenic?

DGKD p.Pro8= (c.24T>A) is classified Likely benign in DGKD (ClinVar, Single submitter, 1 submitter; last evaluated 2018-07-17). Very rare (popmax 0.00891%, nfe).

How common is DGKD p.Pro8= (c.24T>A) in the general population?

DGKD p.Pro8= (c.24T>A) is very rare (popmax 0.00891%, nfe) (gnomAD).

DGKD p.Pro8=

c.24T>A · rs995107287 · VCV753345

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00891%, nfe)

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 1	GERP -2.3, phastCons 1
Overall
CADD	13.94	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00891% European (non-Finnish) · 75/841,848 alleles

Filtering AF 0.00728% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00664%

Overall 0.00751% 75/999,200 alleles · very rare

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.Pro8=
Coding: c.24T>A
MANE Select: NM_152879
dbSNP: rs995107287
Type: single nucleotide variant
Location: chr2:233354542 (GRCh38)
Gene constraint: LOEUF 0.547 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 72.02 · 2 PDB
Residue 8: the 'regulates association with membranes' region; the 'disordered' region

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

Similar variants

DGKD p.Pro8Leu Uncertain significance ★ ⚠ same residue
DGKD c.2375+10A>G Benign ★★ same type
DGKD p.Leu406= Benign ★★ same type
DGKD p.Pro568= Benign/Likely benign ★★ same type
DGKD p.Thr1052= Benign ★★ same type
DGKD p.Ala1047Gly Uncertain significance ★ ⚠ same type
DGKD p.Ala1109Val Uncertain significance ★ ⚠ same type
DGKD p.Ala1134Val 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/dgkd-p-pro8 (accessed [today's date]).

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