Is DGKQ p.Val593Met (c.1777G>A) pathogenic?

DGKQ p.Val593Met (c.1777G>A) is classified Uncertain significance in DGKQ (ClinVar, Single submitter, 1 submitter; last evaluated 2023-08-14). AlphaMissense: likely pathogenic (0.899); Very rare (popmax 0.00167%, amr).

How common is DGKQ p.Val593Met (c.1777G>A) in the general population?

DGKQ p.Val593Met (c.1777G>A) is very rare (popmax 0.00167%, amr) (gnomAD).

What do computational predictors say about DGKQ p.Val593Met (c.1777G>A)?

AlphaMissense predicts likely pathogenic (score 0.899) — an in-silico prediction, not a clinical call.

DGKQ p.Val593Met

c.1777G>A · rs1712025546 · VCV2603209

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.899 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00167%, amr)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.899	likely pathogenic
REVEL	0.338	indeterminate
SaProt	LLR -13.52	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>A here scores Δ0.73 · evaluated, not missing
Constraint at this position
Conservation	phyloP 7.6	GERP 1.7, phastCons 1
Regional constraint	o/e 1.08	unconstrained · MANE · 13 kb · p 0.0021 · regional, not allelic
Overall
CADD	33.0	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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

Grpmax group 0.00167% Admixed American · 1/59,968 alleles

Filtering AF 6.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.9e-05%

Overall 0.000411% 6/1,458,524 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00167%	59,968
Remaining individualsnot grpmax-eligible	0.0016%	62,376
African / African-American	0.00133%	75,048
European (non-Finnish)	0.000255%	392,790

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: DGKQ
Protein: p.Val593Met
Coding: c.1777G>A
MANE Select: NM_001347
dbSNP: rs1712025546
Type: single nucleotide variant
Location: chr4:963248 (GRCh38)
Gene constraint: LOEUF 1.294 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 82.56
Residue 593: the dagkc domain

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

Similar variants

DGKQ c.1367-16G>C Benign ★★ same type
DGKQ c.2316-10C>T Benign ★★ same type
DGKQ p.Asp730= Benign ★★ same type
DGKQ p.Pro55= Benign ★★ same type
DGKQ p.Ala164Thr Uncertain significance ★ ⚠ same type
DGKQ p.Ala228Val Uncertain significance ★ ⚠ same type
DGKQ p.Ala229Gly Uncertain significance ★ ⚠ same type
DGKQ p.Ala247Gly 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/dgkq-p-val593met (accessed [today's date]).

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