Is DGKQ p.Val50Phe (c.148G>T) pathogenic?

DGKQ p.Val50Phe (c.148G>T) is classified Uncertain significance in DGKQ (ClinVar, Single submitter, 1 submitter; last evaluated 2025-10-15). AlphaMissense: likely benign (0.0991); Very rare (popmax 0.0028%, amr).

How common is DGKQ p.Val50Phe (c.148G>T) in the general population?

DGKQ p.Val50Phe (c.148G>T) is very rare (popmax 0.0028%, amr) (gnomAD).

What do computational predictors say about DGKQ p.Val50Phe (c.148G>T)?

AlphaMissense predicts likely benign (score 0.0991) — an in-silico prediction, not a clinical call.

DGKQ p.Val50Phe

c.148G>T · VCV4659816

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0991 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0028%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0991	likely benign
REVEL	0.198	benign-leaning
SaProt	LLR -8.28	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 -0.29	GERP -0.61
Regional constraint	o/e 1.08	unconstrained · MANE · 13 kb · p 0.0021 · regional, not allelic
Overall
CADD	4.619	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

Grpmax group 0.0028% Admixed American · 1/35,662 alleles

Filtering AF 0.000202% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000133%

Overall 0.000572% 8/1,398,430 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0028%	35,662
South Asian	0.00151%	66,320
European (non-Finnish)	0.000562%	177,837

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.Val50Phe
Coding: c.148G>T
MANE Select: NM_001347
Type: single nucleotide variant
Location: chr4:973335 (GRCh38)
Gene constraint: LOEUF 1.294 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 82.56
Residue 50: the 'disordered' region

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-val50phe (accessed [today's date]).

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