Is DGKB p.Pro783Leu (c.2348C>T) pathogenic?

DGKB p.Pro783Leu (c.2348C>T) is classified Uncertain significance in DGKB (ClinVar, Single submitter, 1 submitter; last evaluated 2025-02-20). AlphaMissense: likely benign (0.1614); Very rare (popmax 0.00017%, nfe).

How common is DGKB p.Pro783Leu (c.2348C>T) in the general population?

DGKB p.Pro783Leu (c.2348C>T) is very rare (popmax 0.00017%, nfe) (gnomAD).

What do computational predictors say about DGKB p.Pro783Leu (c.2348C>T)?

AlphaMissense predicts likely benign (score 0.1614) — an in-silico prediction, not a clinical call.

DGKB p.Pro783Leu

c.2348C>T · VCV3839618

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1614 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00017%, nfe)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.1614	likely benign
REVEL	0.625	indeterminate
SaProt	LLR -12.06	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2.2, phastCons 1
Regional constraint	o/e 1.10	unconstrained · MANE · 28 kb · p 0.45 · regional, not allelic
Overall
CADD	26.3	PHRED · no single calibrated threshold — expert panels disagree

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

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM P784L vs ClinVar P783L) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00017% European (non-Finnish) · 2/1,179,558 alleles

Filtering AF 2.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000124% 2/1,613,294 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.Pro783Leu
Coding: c.2348C>T
MANE Select: NM_001350709
Type: single nucleotide variant
Location: chr7:14149195 (GRCh38)
Gene constraint: LOEUF 0.755 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 78.02
Residue 783: the 'required for association with membranes and function in neurite spine formation' region

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-pro783leu (accessed [today's date]).

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