Is DMGDH p.Pro23= (c.69C>T) pathogenic?

DMGDH p.Pro23= (c.69C>T) is classified Likely benign in DMGDH (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-09-26). Ultra-rare (popmax 0.0106%, nfe); Associated with DMGDH-related disorder.

What condition is associated with DMGDH p.Pro23= (c.69C>T)?

DMGDH p.Pro23= (c.69C>T) is associated with DMGDH-related disorder (ClinVar).

How common is DMGDH p.Pro23= (c.69C>T) in the general population?

DMGDH p.Pro23= (c.69C>T) is ultra-rare (popmax 0.0106%, nfe) (gnomAD).

DMGDH p.Pro23=

c.69C>T · rs929359642 · VCV3040607

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0106%, nfe)

Conditions

DMGDH-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -5.4	GERP -4.5
Overall
CADD	5.262	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0106% European (non-Finnish) · 110/1,036,044 alleles

Filtering AF 0.009% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00838%

Overall 0.0115% 152/1,317,760 alleles · ultra-rare exomes 132/1,165,640 · genomes 20/152,120 · joint denominator

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	0.109%	914
European (non-Finnish)grpmax	0.0106%	9,419
African / African-American	0.00306%	32,691

Finnish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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: DMGDH
Protein: p.Pro23=
Coding: c.69C>T
MANE Select: NM_013391
dbSNP: rs929359642
Type: single nucleotide variant
Location: chr5:79069552 (GRCh38)
Gene constraint: LOEUF 0.942 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 95.13 · 1 PDB
Residue 23: the 'disordered' region

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

Disease context

DMGDH-related disorder

Similar variants

DMGDH c.101+10G>T Likely benign same condition
DMGDH c.1814+10C>T Likely benign same condition
DMGDH p.Arg477= Likely benign same condition
DMGDH p.Leu105= Likely benign same condition
DMGDH p.Phe754Ser Benign same condition
DMGDH p.Tyr186Cys Likely benign ⚠ same condition
DMGDH p.His109Arg Likely pathogenic ★★ ⚠ same type
DMGDH p.Arg719Cys 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/dmgdh-p-pro23 (accessed [today's date]).

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