Is DGKD p.Pro12Ser (c.34C>T) pathogenic?

DGKD p.Pro12Ser (c.34C>T) is classified Uncertain significance in DGKD (ClinVar, Single submitter, 1 submitter; last evaluated 2025-10-30). AlphaMissense: likely benign (0.0722); Ultra-rare (popmax 0.0175%, afr).

How common is DGKD p.Pro12Ser (c.34C>T) in the general population?

DGKD p.Pro12Ser (c.34C>T) is ultra-rare (popmax 0.0175%, afr) (gnomAD).

What do computational predictors say about DGKD p.Pro12Ser (c.34C>T)?

AlphaMissense predicts likely benign (score 0.0722) — an in-silico prediction, not a clinical call.

DGKD p.Pro12Ser

c.34C>T · VCV4659743

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0722 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0175%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0722	likely benign
REVEL	0.175	moderately benign-leaning
SaProt	LLR -7.23	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 0.65	GERP -1, phastCons 0.98
Regional constraint	o/e 2.05	unconstrained · MANE · 67 bp · p 3e-08 · regional, not allelic
Overall
CADD	15.78	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.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0175% African / African-American · 10/57,064 alleles

Filtering AF 0.00943% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00723%

Overall 0.00713% 73/1,023,538 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0175%	5,706
Remaining individualsnot grpmax-eligible	0.00967%	10,340
European (non-Finnish)	0.00691%	14,465
South Asian	0.00319%	31,354

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.Pro12Ser
Coding: c.34C>T
MANE Select: NM_152879
Type: single nucleotide variant
Location: chr2:233354552 (GRCh38)
Gene constraint: LOEUF 0.547 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 72.02 · 2 PDB
Residue 12: the 'regulates association with membranes' region; the 'disordered' region

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

Similar variants

DGKD p.Pro12His Uncertain significance ★ ⚠ same residue
DGKD p.Pro12Thr Conflicting classifications of pathogenicity ★ ⚠ same residue
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

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-pro12ser (accessed [today's date]).

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