Is QDPR p.Ser39= (c.117C>T) pathogenic?

QDPR p.Ser39= (c.117C>T) is classified Likely benign in QDPR (ClinVar, Single submitter, 1 submitter; last evaluated 2024-06-24). Very rare (popmax 0.00267%, afr); Associated with dihydropteridine reductase deficiency.

What condition is associated with QDPR p.Ser39= (c.117C>T)?

QDPR p.Ser39= (c.117C>T) is associated with dihydropteridine reductase deficiency (ClinVar).

How common is QDPR p.Ser39= (c.117C>T) in the general population?

QDPR p.Ser39= (c.117C>T) is very rare (popmax 0.00267%, afr) (gnomAD).

QDPR p.Ser39=

Q: How is Hyperphenylalaninemia due to tetrahydrobiopterin deficiency inherited?

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

c.117C>T · rs776939557 · VCV3018227

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00267%, afr)

Conditions

dihydropteridine reductase deficiency

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.072	moderately benign-leaning
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>C here scores Δ0.31 · evaluated, not missing
Constraint at this position
Conservation	phyloP 3.5	GERP -0.52, phastCons 1
Overall
CADD	12.41	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00267% African / African-American · 2/74,866 alleles

Filtering AF 0.0013% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00108%

Overall 0.0018% 29/1,613,470 alleles · very rare

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	0.00313%	31,998
African / African-Americangrpmax	0.00267%	37,433
South Asian	0.0022%	45,539
European (non-Finnish)	0.00195%	51,289

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: QDPR
Protein: p.Ser39=
Coding: c.117C>T
MANE Select: NM_000320
dbSNP: rs776939557
Type: single nucleotide variant
Location: chr4:17509352 (GRCh38)
Gene constraint: LOEUF 0.984 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 96.43 · 2 PDB
Residue 39: a β-strand

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 p.Ser39Arg Uncertain significance ★★ ⚠ same residue
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

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-ser39 (accessed [today's date]).

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