Is QDPR p.Cys161Phe (c.482G>T) pathogenic?

QDPR p.Cys161Phe (c.482G>T) is classified Uncertain significance in QDPR (ClinVar, Multiple submitters, 2 submitters; last evaluated 2026-03-20). AlphaMissense: likely pathogenic (0.8699); Very rare (popmax 0.00167%, amr); Associated with dihydropteridine reductase deficiency.

What condition is associated with QDPR p.Cys161Phe (c.482G>T)?

QDPR p.Cys161Phe (c.482G>T) is associated with dihydropteridine reductase deficiency (ClinVar).

How common is QDPR p.Cys161Phe (c.482G>T) in the general population?

QDPR p.Cys161Phe (c.482G>T) is very rare (popmax 0.00167%, amr) (gnomAD).

What do computational predictors say about QDPR p.Cys161Phe (c.482G>T)?

AlphaMissense predicts likely pathogenic (score 0.8699) — an in-silico prediction, not a clinical call.

QDPR p.Cys161Phe

Q: How is Hyperphenylalaninemia due to tetrahydrobiopterin deficiency inherited?

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

c.482G>T · rs1384853803 · VCV2967634

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.8699 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00167%, amr)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

dihydropteridine reductase deficiency

Computational evidence

Protein change
AlphaMissense	0.8699	likely pathogenic
REVEL	0.876	moderately pathogenic-leaning
SaProt	LLR -11.96	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 7.4	GERP 2.4, phastCons 1
Regional constraint	o/e 1.00	unconstrained · MANE · 25 kb · p 0.99 · regional, not allelic
Overall
CADD	28.2	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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 0.00167% Admixed American · 1/60,030 alleles

Overall 6.2e-05% 1/1,614,206 alleles · very rare exomes 1/1,461,866 · genomes 0/152,340 · joint denominator

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.Cys161Phe
Coding: c.482G>T
MANE Select: NM_000320
dbSNP: rs1384853803
Type: single nucleotide variant
Location: chr4:17492295 (GRCh38)
Gene constraint: LOEUF 0.984 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 96.43 · 2 PDB
Residue 161: 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 p.Cys161= Likely benign ★ 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-cys161phe (accessed [today's date]).

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