Is DGKB p.Val246Leu (c.736G>T) pathogenic?

DGKB p.Val246Leu (c.736G>T) is classified Uncertain significance in DGKB (ClinVar, Single submitter, 1 submitter; last evaluated 2025-05-01). AlphaMissense: likely benign (0.2424); Very rare (popmax 0.00167%, amr).

How common is DGKB p.Val246Leu (c.736G>T) in the general population?

DGKB p.Val246Leu (c.736G>T) is very rare (popmax 0.00167%, amr) (gnomAD).

What do computational predictors say about DGKB p.Val246Leu (c.736G>T)?

AlphaMissense predicts likely benign (score 0.2424) — an in-silico prediction, not a clinical call.

DGKB p.Val246Leu

c.736G>T · VCV4011118

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2424 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00167%, amr)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.2424	likely benign
REVEL	0.444	indeterminate
SaProt	LLR -8.03	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 2, phastCons 1
Regional constraint	o/e 0.95	unconstrained · MANE · 663 kb · p 0.15 · regional, not allelic
Overall
CADD	24.1	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 0.00167% Admixed American · 1/60,018 alleles

Overall 6.84e-05% 1/1,461,360 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: DGKB
Protein: p.Val246Leu
Coding: c.736G>T
MANE Select: NM_001350709
Type: single nucleotide variant
Location: chr7:14685338 (GRCh38)
Gene constraint: LOEUF 0.755 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 78.02

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

Similar variants

DGKB p.Ala115Thr Uncertain significance ★ ⚠ same type
DGKB p.Ala417Thr Uncertain significance ★ ⚠ same type
DGKB p.Arg110Ile Uncertain significance ★ ⚠ same type
DGKB p.Arg120Gln Uncertain significance ★ ⚠ same type
DGKB p.Arg530Gly Uncertain significance ★ ⚠ same type
DGKB p.Asn412Asp Uncertain significance ★ ⚠ same type
DGKB p.Asp423Glu Uncertain significance ★ ⚠ same type
DGKB p.Asp59Gly 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/dgkb-p-val246leu (accessed [today's date]).

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