Is QDPR p.Ala64Ser (c.190G>T) pathogenic?

QDPR p.Ala64Ser (c.190G>T) is classified Uncertain significance in QDPR (ClinVar, Single submitter, 1 submitter; last evaluated 2024-05-15). AlphaMissense: likely benign (0.1627); Absent from gnomAD v4.1; Associated with dihydropteridine reductase deficiency.

What condition is associated with QDPR p.Ala64Ser (c.190G>T)?

QDPR p.Ala64Ser (c.190G>T) is associated with dihydropteridine reductase deficiency (ClinVar).

How common is QDPR p.Ala64Ser (c.190G>T) in the general population?

QDPR p.Ala64Ser (c.190G>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about QDPR p.Ala64Ser (c.190G>T)?

AlphaMissense predicts likely benign (score 0.1627) — an in-silico prediction, not a clinical call.

QDPR p.Ala64Ser

Q: How is Hyperphenylalaninemia due to tetrahydrobiopterin deficiency inherited?

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

c.190G>T · rs1480794443 · VCV1445275

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1627 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

dihydropteridine reductase deficiency

Computational evidence

Protein change
AlphaMissense	0.1627	likely benign
REVEL	0.377	indeterminate
SaProt	LLR -6.43	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.3	GERP 2.3, phastCons 1
Regional constraint	o/e 1.00	unconstrained · MANE · 25 kb · p 0.99 · regional, not allelic
Overall
CADD	21.8	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: QDPR
Protein: p.Ala64Ser
Coding: c.190G>T
MANE Select: NM_000320
dbSNP: rs1480794443
Type: single nucleotide variant
Location: chr4:17509279 (GRCh38)
Gene constraint: LOEUF 0.984 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 96.43 · 2 PDB
Residue 64: 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.Ala64= Likely benign ★ same residue
QDPR p.Ala64Pro 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

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-ala64ser (accessed [today's date]).

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