Is DGKD p.Pro17Ala (c.49C>G) pathogenic?

DGKD p.Pro17Ala (c.49C>G) is classified Uncertain significance in DGKD (ClinVar, Single submitter, 1 submitter; last evaluated 2023-02-01). AlphaMissense: likely benign (0.0511); Absent from gnomAD v4.1.

How common is DGKD p.Pro17Ala (c.49C>G) in the general population?

DGKD p.Pro17Ala (c.49C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about DGKD p.Pro17Ala (c.49C>G)?

AlphaMissense predicts likely benign (score 0.0511) — an in-silico prediction, not a clinical call.

DGKD p.Pro17Ala

c.49C>G · rs763301780 · VCV2480360

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0511 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,061,692)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0511	likely benign
REVEL	0.135	moderately benign-leaning
SaProt	LLR -8.14	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.8	GERP 0.13, phastCons 1
Regional constraint	o/e 2.05	unconstrained · MANE · 67 bp · p 3e-08 · regional, not allelic
Overall
CADD	14.44	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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

Population frequency

gnomAD v4.1 · exomes + genomes

No allele count reported in gnomAD v4.1 (AN 1,061,692). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: DGKD
Protein: p.Pro17Ala
Coding: c.49C>G
MANE Select: NM_152879
dbSNP: rs763301780
Type: single nucleotide variant
Location: chr2:233354567 (GRCh38)
Gene constraint: LOEUF 0.547 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 72.02 · 2 PDB
Residue 17: 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.Pro17Thr Uncertain significance ★ ⚠ same residue
DGKD p.Pro17= Likely benign ★ 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

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-pro17ala (accessed [today's date]).

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