Is DGKB p.Val395Ala (c.1184T>C) pathogenic?

DGKB p.Val395Ala (c.1184T>C) is classified Uncertain significance in DGKB (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-25). AlphaMissense: likely benign (0.0999); Very rare (popmax 0.00017%, nfe).

How common is DGKB p.Val395Ala (c.1184T>C) in the general population?

DGKB p.Val395Ala (c.1184T>C) is very rare (popmax 0.00017%, nfe) (gnomAD).

What do computational predictors say about DGKB p.Val395Ala (c.1184T>C)?

AlphaMissense predicts likely benign (score 0.0999) — an in-silico prediction, not a clinical call.

DGKB p.Val395Ala

c.1184T>C · VCV4011115

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0999 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00017%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0999	likely benign
REVEL	0.171	moderately benign-leaning
SaProt	LLR -6.91	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 3.9	GERP -1.3, phastCons 1
Regional constraint	o/e 0.95	unconstrained · MANE · 663 kb · p 0.15 · regional, not allelic
Overall
CADD	20.5	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.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM V396A vs ClinVar V395A) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00017% European (non-Finnish) · 2/1,175,098 alleles

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

Overall 0.000125% 2/1,604,742 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.Val395Ala
Coding: c.1184T>C
MANE Select: NM_001350709
Type: single nucleotide variant
Location: chr7:14621478 (GRCh38)
Gene constraint: LOEUF 0.755 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 78.02
Residue 395: the 'disordered' 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-val395ala (accessed [today's date]).

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