Is DGUOK p.Ser52Phe (c.155C>T) pathogenic?

DGUOK p.Ser52Phe (c.155C>T) is classified Pathogenic/Likely pathogenic in DGUOK (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-10-05). AlphaMissense: likely pathogenic (0.9778); Very rare (popmax 0.000933%, nfe); Associated with DGUOK-related disorder.

What condition is associated with DGUOK p.Ser52Phe (c.155C>T)?

DGUOK p.Ser52Phe (c.155C>T) is associated with DGUOK-related disorder, mitochondrial DNA depletion syndrome 3 (hepatocerebral type) (ClinVar).

How common is DGUOK p.Ser52Phe (c.155C>T) in the general population?

DGUOK p.Ser52Phe (c.155C>T) is very rare (popmax 0.000933%, nfe) (gnomAD).

What do computational predictors say about DGUOK p.Ser52Phe (c.155C>T)?

AlphaMissense predicts likely pathogenic (score 0.9778) — an in-silico prediction, not a clinical call.

DGUOK p.Ser52Phe

c.155C>T · rs1204316787 · VCV488490

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely pathogenic

0.9778 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000933%, nfe)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

DGUOK-related disorder

Computational evidence

Protein change
AlphaMissense	0.9778	likely pathogenic ✓ concordant with ClinVar · top 2% in DGUOK
REVEL	0.977	strongly pathogenic-leaning
SaProt	LLR -15.98	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 2.3, phastCons 1
Regional constraint	o/e 1.07	unconstrained · MANE · 32 kb · p 0.18 · regional, not allelic
Overall
CADD	32.0	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 0.000933% European (non-Finnish) · 11/1,179,006 alleles

Filtering AF 0.000501% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000366%

Overall 0.000682% 11/1,612,854 alleles · very rare

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: DGUOK
Protein: p.Ser52Phe
Coding: c.155C>T
MANE Select: NM_080916
dbSNP: rs1204316787
Type: single nucleotide variant
Location: chr2:73938922 (GRCh38)
Gene constraint: LOEUF 1.115 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 87.27 · 1 PDB
Residue 52: a binding site; an α-helix

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

Disease context

DGUOK-related disorder

Also linked: mitochondrial DNA depletion syndrome 3 (hepatocerebral type)

Similar variants

DGUOK p.Ser52Cys Uncertain significance ★ ⚠ same residue
DGUOK p.Ser52= Likely benign ★ same residue
DGUOK c.444-62C>A Pathogenic/Likely pathogenic ★★ same condition
DGUOK p.Arg118His Pathogenic/Likely pathogenic ★★ same condition
DGUOK p.Arg142Lys Pathogenic/Likely pathogenic ★★ same condition
DGUOK p.Asp255Tyr Pathogenic/Likely pathogenic ★★ ⚠ same condition
DGUOK p.Gln197= Pathogenic/Likely pathogenic ★★ same condition
DGUOK p.Gln79Ter Pathogenic ★★ same condition

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/dguok-p-ser52phe (accessed [today's date]).

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