Is DMGDH p.Pro4Arg (c.11C>G) pathogenic?

DMGDH p.Pro4Arg (c.11C>G) is classified Uncertain significance in DMGDH (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-11). AlphaMissense: likely benign (0.0388); Very rare (popmax 0.00688%, sas).

How common is DMGDH p.Pro4Arg (c.11C>G) in the general population?

DMGDH p.Pro4Arg (c.11C>G) is very rare (popmax 0.00688%, sas) (gnomAD).

What do computational predictors say about DMGDH p.Pro4Arg (c.11C>G)?

AlphaMissense predicts likely benign (score 0.0388) — an in-silico prediction, not a clinical call.

DMGDH p.Pro4Arg

c.11C>G · VCV4012253

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0388 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00688%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0388	likely benign
REVEL	0.097	moderately benign-leaning
SaProt	LLR -6.13	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 -7	GERP -4.2
Regional constraint	o/e 0.94	unconstrained · MANE · 72 kb · p 0.036 · regional, not allelic
Overall
CADD	0.103	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 0.00688% South Asian · 4/58,124 alleles

Filtering AF 0.00231% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00138%

Overall 0.00124% 17/1,374,896 alleles · very rare exomes 17/1,222,818 · genomes 0/152,078 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00688%	14,531
European (non-Finnish)	0.00122%	81,724

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.Pro4Arg
Coding: c.11C>G
MANE Select: NM_013391
Type: single nucleotide variant
Location: chr5:79069610 (GRCh38)
Gene constraint: LOEUF 0.942 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 95.13 · 1 PDB

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

Similar variants

DMGDH p.His109Arg Likely pathogenic ★★ ⚠ same type
DMGDH p.Arg719Cys Uncertain significance ★★ ⚠ same type
DMGDH c.101+143A>T Likely benign ★★ same type
DMGDH c.102-4C>T Likely benign ★★ same type
DMGDH c.1518-4T>A Benign/Likely benign ★★ same type
DMGDH c.1684-22A>G Benign/Likely benign ★★ same type
DMGDH c.1815-9A>G Benign ★★ same type
DMGDH c.2250+135T>C Likely benign ★★ 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-pro4arg (accessed [today's date]).

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