Is PNP p.Phe85= (c.255C>T) pathogenic?

PNP p.Phe85= (c.255C>T) is classified Likely benign in PNP (ClinVar, Single submitter, 1 submitter; last evaluated 2025-06-29). Very rare (popmax 0.000678%, nfe); Associated with purine nucleoside phosphorylase deficiency.

What condition is associated with PNP p.Phe85= (c.255C>T)?

PNP p.Phe85= (c.255C>T) is associated with purine nucleoside phosphorylase deficiency (ClinVar).

How common is PNP p.Phe85= (c.255C>T) in the general population?

PNP p.Phe85= (c.255C>T) is very rare (popmax 0.000678%, nfe) (gnomAD).

How is Purine nucleoside phosphorylase deficiency inherited?

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

PNP p.Phe85=

c.255C>T · VCV4720059

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.000678%, nfe)

Conditions

purine nucleoside phosphorylase deficiency

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.1	GERP 0.99, phastCons 1
Overall
CADD	10.73	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000678% European (non-Finnish) · 8/1,180,008 alleles

Filtering AF 0.000292% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000211%

Overall 0.000496% 8/1,614,080 alleles · very rare exomes 8/1,461,862 · genomes 0/152,218 · 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: PNP
Protein: p.Phe85=
Coding: c.255C>T
MANE Select: NM_000270
Type: single nucleotide variant
Location: chr14:20474545 (GRCh38)
Gene constraint: LOEUF 0.995 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 94.13 · 41 PDB
Residue 85: a binding site

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

Disease context

purine nucleoside phosphorylase deficiency — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Purine nucleoside phosphorylase deficiency (Orphanet):

Inheritance: Autosomal recessive
Onset: Adolescent, Childhood, Infancy

Similar variants

PNP p.Phe85Leu Uncertain significance ★ ⚠ same residue
PNP c.12-1G>C Pathogenic/Likely pathogenic ★★ same condition
PNP c.286-18G>A Pathogenic/Likely pathogenic ★★ same condition
PNP p.Ala174Pro Likely pathogenic ★★ same condition
PNP p.Arg234Pro Pathogenic/Likely pathogenic ★★ same condition
PNP p.Arg24Ter Pathogenic ★★ same condition
PNP p.Arg67Ter Pathogenic ★★ same condition
PNP p.Asp128Gly 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/pnp-p-phe85 (accessed [today's date]).

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