Is PCBD1 p.Cys82Arg (c.244T>C) pathogenic?

PCBD1 p.Cys82Arg (c.244T>C) is classified Likely pathogenic in PCBD1 (ClinVar, Single submitter, 2 submitters; last evaluated 2022-02-02). AlphaMissense: likely pathogenic (0.8179); Very rare (popmax 0.00186%, nfe); Associated with pterin-4 alpha-carbinolamine dehydratase 1 deficiency.

What condition is associated with PCBD1 p.Cys82Arg (c.244T>C)?

PCBD1 p.Cys82Arg (c.244T>C) is associated with pterin-4 alpha-carbinolamine dehydratase 1 deficiency (ClinVar).

How common is PCBD1 p.Cys82Arg (c.244T>C) in the general population?

PCBD1 p.Cys82Arg (c.244T>C) is very rare (popmax 0.00186%, nfe) (gnomAD).

What do computational predictors say about PCBD1 p.Cys82Arg (c.244T>C)?

AlphaMissense predicts likely pathogenic (score 0.8179) — an in-silico prediction, not a clinical call.

PCBD1 p.Cys82Arg

Q: How is Hyperphenylalaninemia due to tetrahydrobiopterin deficiency inherited?

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

c.244T>C · rs104894177 · VCV16796

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.8179 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00186%, nfe)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

pterin-4 alpha-carbinolamine dehydratase 1 deficiency

Computational evidence

Protein change
AlphaMissense	0.8179	likely pathogenic ✓ concordant with ClinVar
REVEL	0.811	moderately pathogenic-leaning
SaProt	LLR -13.22	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 11	GERP 1.9, phastCons 1
Regional constraint	o/e 0.66	unconstrained · MANE · 4,580 bp · p 0.00011 · regional, not allelic
Overall
CADD	25.2	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 0.00186% European (non-Finnish) · 22/1,180,014 alleles

Filtering AF 0.00122% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00104%

Overall 0.00136% 22/1,614,078 alleles · very rare exomes 22/1,461,794 · genomes 0/152,284 · 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: PCBD1
Protein: p.Cys82Arg
Coding: c.244T>C
MANE Select: NM_000281
dbSNP: rs104894177
Type: single nucleotide variant
Location: chr10:70884021 (GRCh38)
Gene constraint: LOEUF 1.685 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 96.55
Residue 82: a UniProt-annotated variant site (in hpabh4d; reduced protein levels; loss of hnf1b interaction; loss of hnf1b-coactivator activity); a UniProt-annotated variant site (in hpabh4d; increased proteolytic degradation; reduced dehydratase activity; no impact on hydroxytetrahydrobiopterin-binding; reduced interaction with hnf1b; partial impact on hnf1b-coactivator activity)

Full PCBD1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

pterin-4 alpha-carbinolamine dehydratase 1 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

PCBD1 p.Cys82= Likely benign ★ same residue
PCBD1 p.Gln98Ter Pathogenic/Likely pathogenic ★★ same condition
PCBD1 p.Glu87Ter Pathogenic/Likely pathogenic ★★ same condition
PCBD1 p.Glu97Lys Pathogenic/Likely pathogenic ★★ same condition
PCBD1 p.Arg13Trp Uncertain significance ★★ ⚠ same condition
PCBD1 p.Arg31Cys Uncertain significance ★★ ⚠ same condition
PCBD1 p.Arg88Trp Uncertain significance ★★ ⚠ same condition
PCBD1 p.Asp61Tyr Uncertain significance ★★ ⚠ 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/pcbd1-p-cys82arg (accessed [today's date]).

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