Is DGKD p.Pro12Thr (c.34C>A) pathogenic?

DGKD p.Pro12Thr (c.34C>A) is classified Conflicting classifications of pathogenicity in DGKD (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2024-01-23). AlphaMissense: likely benign (0.0798); Rare (popmax 0.343%, afr).

How common is DGKD p.Pro12Thr (c.34C>A) in the general population?

DGKD p.Pro12Thr (c.34C>A) is rare (popmax 0.343%, afr) (gnomAD).

What do computational predictors say about DGKD p.Pro12Thr (c.34C>A)?

AlphaMissense predicts likely benign (score 0.0798) — an in-silico prediction, not a clinical call.

DGKD p.Pro12Thr

c.34C>A · rs747669327 · VCV734116

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0798 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.343%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0798	likely benign
REVEL	0.182	moderately benign-leaning
SaProt	LLR -8.40	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	15.99	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 0.343% African / African-American · 196/57,130 alleles

Filtering AF 0.304% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.289%

Overall 0.0204% 209/1,023,558 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.343%	291
Middle Eastern	0.048%	2,084
Admixed American	0.0282%	3,547
Remaining individualsnot grpmax-eligible	0.0193%	5,173
European (non-Finnish)	0.000117%	853,417

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.Pro12Thr
Coding: c.34C>A
MANE Select: NM_152879
dbSNP: rs747669327
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.Pro12Ser Uncertain significance ★ ⚠ 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-pro12thr (accessed [today's date]).

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