Is DGKE p.Arg63Pro (c.188G>C) pathogenic?

DGKE p.Arg63Pro (c.188G>C) is classified Likely pathogenic in DGKE (ClinVar, Single submitter, 2 submitters; last evaluated 2025-09-26). AlphaMissense: likely pathogenic (0.8304); Absent from gnomAD v4.1; Associated with atypical hemolytic-uremic syndrome.

What condition is associated with DGKE p.Arg63Pro (c.188G>C)?

DGKE p.Arg63Pro (c.188G>C) is associated with atypical hemolytic-uremic syndrome, hemolytic uremic syndrome, atypical, susceptibility to, 7 (ClinVar).

How common is DGKE p.Arg63Pro (c.188G>C) in the general population?

DGKE p.Arg63Pro (c.188G>C) is absent from gnomAD v4.1 (gnomAD).

How is Atypical hemolytic uremic syndrome inherited?

Typically Autosomal dominant, Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

What do computational predictors say about DGKE p.Arg63Pro (c.188G>C)?

AlphaMissense predicts likely pathogenic (score 0.8304) — an in-silico prediction, not a clinical call.

DGKE p.Arg63Pro

c.188G>C · rs312262694 · VCV50788

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.8304 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

atypical hemolytic-uremic syndrome

Computational evidence

Protein change
AlphaMissense	0.8304	likely pathogenic ✓ concordant with ClinVar
REVEL	0.629	indeterminate
SaProt	LLR -15.32	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.053	GERP -2.6
Regional constraint	o/e 0.93	unconstrained · MANE · 28 kb · p 0.051 · regional, not allelic
Overall
CADD	17.78	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: DGKE
Protein: p.Arg63Pro
Coding: c.188G>C
MANE Select: NM_003647
dbSNP: rs312262694
Type: single nucleotide variant
Location: chr17:56834983 (GRCh38)
Gene constraint: LOEUF 0.995 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 86.18
Residue 63: a UniProt-annotated variant site (in ahus7)

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

Disease context

atypical hemolytic-uremic syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: hemolytic uremic syndrome, atypical, susceptibility to, 7

For Atypical hemolytic uremic syndrome (Orphanet):

Inheritance: Autosomal dominant, Autosomal recessive, Not applicable
Onset: All ages
Prevalence: 1-9 / 1 000 000 (United States)

Similar variants

DGKE p.Arg63Gly Uncertain significance ★ ⚠ same residue
DGKE c.465-2A>G Pathogenic/Likely pathogenic ★★ same condition
DGKE c.889-1G>A Pathogenic ★★ same condition
DGKE p.Gln143Ter Pathogenic ★★ same condition
DGKE p.Trp322Ter Pathogenic ★★ same condition
DGKE p.Asp103Glu Uncertain significance ★★ ⚠ same condition
DGKE p.Leu266= Benign/Likely benign ★★ same condition
DGKE c.1524+2T>C Pathogenic ★ 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/dgke-p-arg63pro (accessed [today's date]).

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