Is QDPR p.Ser200Arg (c.600C>G) pathogenic?

QDPR p.Ser200Arg (c.600C>G) is classified Uncertain significance in QDPR (ClinVar, Multiple submitters, 3 submitters; last evaluated 2024-10-31). AlphaMissense: ambiguous (0.372); Rare (popmax 0.188%, afr); Associated with dihydropteridine reductase deficiency.

What condition is associated with QDPR p.Ser200Arg (c.600C>G)?

QDPR p.Ser200Arg (c.600C>G) is associated with dihydropteridine reductase deficiency (ClinVar).

How common is QDPR p.Ser200Arg (c.600C>G) in the general population?

QDPR p.Ser200Arg (c.600C>G) is rare (popmax 0.188%, afr) (gnomAD).

What do computational predictors say about QDPR p.Ser200Arg (c.600C>G)?

AlphaMissense predicts ambiguous (score 0.372) — an in-silico prediction, not a clinical call.

QDPR p.Ser200Arg

Q: How is Hyperphenylalaninemia due to tetrahydrobiopterin deficiency inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

c.600C>G · rs112242659 · VCV1003665

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

ambiguous

0.372 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.188%, afr)

Conditions

dihydropteridine reductase deficiency

Computational evidence

Protein change
AlphaMissense	0.372	ambiguous
REVEL	0.407	indeterminate
SaProt	LLR -11.70	damaging
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.1	GERP -0.64, phastCons 1
Regional constraint	o/e 1.00	unconstrained · MANE · 25 kb · p 0.99 · regional, not allelic
Overall
CADD	23.0	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 0.188% African / African-American · 141/75,046 alleles

Filtering AF 0.163% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.153%

Overall 0.0113% 182/1,614,040 alleles · rare exomes 92/1,461,718 · genomes 90/152,322 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.188%	532
Admixed American	0.0367%	2,728
Remaining individualsnot grpmax-eligible	0.0272%	3,677
South Asian	0.0011%	91,068
European (non-Finnish)	8.48e-05%	1,179,915

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: QDPR
Protein: p.Ser200Arg
Coding: c.600C>G
MANE Select: NM_000320
dbSNP: rs112242659
Type: single nucleotide variant
Location: chr4:17490691 (GRCh38)
Gene constraint: LOEUF 0.984 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 96.43 · 2 PDB
Residue 200: an α-helix

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

Disease context

dihydropteridine reductase deficiency — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Hyperphenylalaninemia due to tetrahydrobiopterin deficiency (Orphanet):

Inheritance: Autosomal recessive
Onset: Infancy, Neonatal
Prevalence: 1-9 / 1 000 000 (Japan)

Similar variants

QDPR c.436+2552A>G Pathogenic ★★ same condition
QDPR c.545+1G>A Pathogenic ★★ same condition
QDPR c.546-1G>A Likely pathogenic ★★ same condition
QDPR p.Arg221Ter Pathogenic ★★ same condition
QDPR p.His158Tyr Pathogenic/Likely pathogenic ★★ same condition
QDPR p.Phe212Ser Likely pathogenic ★★ same condition
QDPR p.Ser115Leu Pathogenic/Likely pathogenic ★★ same condition
QDPR p.Tyr150Cys 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/qdpr-p-ser200arg (accessed [today's date]).

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