Is DGKD p.Thr552Ser (c.1655C>G) pathogenic?

DGKD p.Thr552Ser (c.1655C>G) is classified Uncertain significance in DGKD (ClinVar, Single submitter, 1 submitter; last evaluated 2022-07-14). AlphaMissense: likely pathogenic (0.7077); Very rare (popmax 0.00204%, nfe).

How common is DGKD p.Thr552Ser (c.1655C>G) in the general population?

DGKD p.Thr552Ser (c.1655C>G) is very rare (popmax 0.00204%, nfe) (gnomAD).

What do computational predictors say about DGKD p.Thr552Ser (c.1655C>G)?

AlphaMissense predicts likely pathogenic (score 0.7077) — an in-silico prediction, not a clinical call.

DGKD p.Thr552Ser

c.1655C>G · rs1172873512 · VCV2298549

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7077 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00204%, nfe)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.7077	likely pathogenic
REVEL	0.306	indeterminate
SaProt	LLR -7.76	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 1.9, phastCons 1
Regional constraint	o/e 0.92	unconstrained · MANE · 9,086 bp · p 0.08 · regional, not allelic
Overall
CADD	23.7	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 0.00204% European (non-Finnish) · 24/1,176,174 alleles

Filtering AF 0.00138% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00116%

Overall 0.00155% 25/1,609,014 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00204%	49,007
Remaining individualsnot grpmax-eligible	0.00161%	62,228

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.Thr552Ser
Coding: c.1655C>G
MANE Select: NM_152879
dbSNP: rs1172873512
Type: single nucleotide variant
Location: chr2:233449143 (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-thr552ser (accessed [today's date]).

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