Is DGKH p.Arg85Pro (c.254G>C) pathogenic?

DGKH p.Arg85Pro (c.254G>C) is classified Uncertain significance in DGKH (ClinVar, Single submitter, 1 submitter; last evaluated 2023-05-08). AlphaMissense: likely pathogenic (0.9995); Absent from gnomAD v4.1.

How common is DGKH p.Arg85Pro (c.254G>C) in the general population?

DGKH p.Arg85Pro (c.254G>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about DGKH p.Arg85Pro (c.254G>C)?

AlphaMissense predicts likely pathogenic (score 0.9995) — an in-silico prediction, not a clinical call.

DGKH p.Arg85Pro

c.254G>C · rs201753254 · VCV2545125

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9995 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9995	likely pathogenic · top 2% in DGKH
REVEL	0.772	pathogenic-leaning
SaProt	LLR -15.67	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 12	GERP 1.8, phastCons 1
Regional constraint	o/e 1.03	unconstrained · MANE · 79 kb · p 0.74 · regional, not allelic
Overall
CADD	33.0	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: DGKH
Protein: p.Arg85Pro
Coding: c.254G>C
MANE Select: NM_178009
dbSNP: rs201753254
Type: single nucleotide variant
Location: chr13:42127524 (GRCh38)
Gene constraint: LOEUF 0.689 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 71.33
Residue 85: the ph domain

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

Similar variants

DGKH p.Arg85Leu Uncertain significance ★ ⚠ same residue
DGKH p.Ala113Val Uncertain significance ★ ⚠ same type
DGKH p.Ala118Thr Uncertain significance ★ ⚠ same type
DGKH p.Ala19Ser Uncertain significance ★ ⚠ same type
DGKH p.Ala506Thr Uncertain significance ★ ⚠ same type
DGKH p.Ala627Thr Uncertain significance ★ ⚠ same type
DGKH p.Ala673Val Uncertain significance ★ ⚠ same type
DGKH p.Ala981Thr 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/dgkh-p-arg85pro (accessed [today's date]).

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