Is DGKD p.Phe342Leu (c.1026C>G) pathogenic?

DGKD p.Phe342Leu (c.1026C>G) is classified Uncertain significance in DGKD (ClinVar, Single submitter, 1 submitter; last evaluated 2025-10-17). AlphaMissense: likely pathogenic (0.9965); Absent from gnomAD v4.1.

How common is DGKD p.Phe342Leu (c.1026C>G) in the general population?

DGKD p.Phe342Leu (c.1026C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about DGKD p.Phe342Leu (c.1026C>G)?

AlphaMissense predicts likely pathogenic (score 0.9965) — an in-silico prediction, not a clinical call.

DGKD p.Phe342Leu

c.1026C>G · VCV4659753

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9965 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.9965	likely pathogenic · top 9% in DGKD
REVEL	0.343	indeterminate
SaProt	LLR -14.11	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.25	GERP -2.4, phastCons 0.98
Regional constraint	o/e 0.50	unconstrained · MANE · 7,389 bp · p 1.7e-07 · regional, not allelic
Overall
CADD	23.7	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: DGKD
Protein: p.Phe342Leu
Coding: c.1026C>G
MANE Select: NM_152879
Type: single nucleotide variant
Location: chr2:233438320 (GRCh38)
Gene constraint: LOEUF 0.547 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 72.02 · 2 PDB
Residue 342: the dagkc domain

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

Similar variants

DGKD c.2375+10A>G Benign ★★ same type
DGKD p.Leu406= Benign ★★ same type
DGKD p.Pro568= Benign/Likely benign ★★ same type
DGKD p.Thr1052= Benign ★★ same type
DGKD p.Ala1047Gly Uncertain significance ★ ⚠ same type
DGKD p.Ala1109Val Uncertain significance ★ ⚠ same type
DGKD p.Ala1134Val Uncertain significance ★ ⚠ same type
DGKD p.Ala1140Gly 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/dgkd-p-phe342leu (accessed [today's date]).

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