Is DGKD p.Ser460Phe (c.1379C>T) pathogenic?

DGKD p.Ser460Phe (c.1379C>T) is classified Uncertain significance in DGKD (ClinVar, Single submitter, 1 submitter; last evaluated 2023-06-29). AlphaMissense: likely benign (0.1403); Very rare (popmax 0.00356%, nfe).

How common is DGKD p.Ser460Phe (c.1379C>T) in the general population?

DGKD p.Ser460Phe (c.1379C>T) is very rare (popmax 0.00356%, nfe) (gnomAD).

What do computational predictors say about DGKD p.Ser460Phe (c.1379C>T)?

AlphaMissense predicts likely benign (score 0.1403) — an in-silico prediction, not a clinical call.

DGKD p.Ser460Phe

c.1379C>T · rs375904433 · VCV2608773

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1403 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00356%, nfe)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.1403	likely benign
REVEL	0.593	indeterminate
SaProt	LLR -12.84	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 4.8	GERP 1.7, phastCons 0.91
Regional constraint	o/e 0.92	unconstrained · MANE · 9,086 bp · p 0.08 · regional, not allelic
Overall
CADD	25.6	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00356% European (non-Finnish) · 42/1,180,052 alleles

Filtering AF 0.00267% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00236%

Overall 0.00266% 43/1,614,120 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00356%	28,096
African / African-American	0.00133%	74,952

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: DGKD
Protein: p.Ser460Phe
Coding: c.1379C>T
MANE Select: NM_152879
dbSNP: rs375904433
Type: single nucleotide variant
Location: chr2:233446756 (GRCh38)
Gene constraint: LOEUF 0.547 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 72.02 · 2 PDB

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-ser460phe (accessed [today's date]).

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