Is PTRH2 p.Gln85Pro (c.254A>C) pathogenic?

PTRH2 p.Gln85Pro (c.254A>C) is classified Pathogenic in PTRH2 (ClinVar, Multiple submitters, 6 submitters; last evaluated 2024-03-17). AlphaMissense: likely pathogenic (0.8852); Absent from gnomAD v4.1; Associated with neurologic, endocrine, and pancreatic disease, multisystem, infantile-onset 1.

How common is PTRH2 p.Gln85Pro (c.254A>C) in the general population?

PTRH2 p.Gln85Pro (c.254A>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about PTRH2 p.Gln85Pro (c.254A>C)?

AlphaMissense predicts likely pathogenic (score 0.8852) — an in-silico prediction, not a clinical call.

PTRH2 p.Gln85Pro

Q: What condition is associated with PTRH2 p.Gln85Pro (c.254A>C)?

PTRH2 p.Gln85Pro (c.254A>C) is associated with neurologic, endocrine, and pancreatic disease, multisystem, infantile-onset 1, cerebellar ataxia, hearing loss disorder (ClinVar).

Q: How is Infantile multisystem neurologic-endocrine-pancreatic disease inherited?

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

c.254A>C · rs730882234 · VCV183332

Pathogenic Multiple submitters

Classification

Pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

AlphaMissense

likely pathogenic

0.8852 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

neurologic, endocrine, and pancreatic disease, multisystem, infantile-onset 1

Computational evidence

Protein change
AlphaMissense	0.8852	likely pathogenic ✓ concordant with ClinVar
REVEL	0.808	moderately pathogenic-leaning
SaProt	LLR -16.08	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 7.9	GERP 1.8, phastCons 1
Regional constraint	o/e 0.82	unconstrained · MANE · 536 bp · p 0.0092 · regional, not allelic
Overall
CADD	27.6	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

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: PTRH2
Protein: p.Gln85Pro
Coding: c.254A>C
MANE Select: NM_016077
dbSNP: rs730882234
Type: single nucleotide variant
Location: chr17:59697725 (GRCh38)
Gene constraint: LOEUF 1.322 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 84.10 · 1 PDB
Residue 85: a UniProt-annotated variant site (in imnepd1); an α-helix

Full PTRH2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

neurologic, endocrine, and pancreatic disease, multisystem, infantile-onset 1 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: cerebellar ataxia hearing loss disorder neurologic, endocrine, and pancreatic disease, multisystem, infantile-onset

For Infantile multisystem neurologic-endocrine-pancreatic disease (Orphanet):

Inheritance: Autosomal recessive
Onset: Infancy

Similar variants

PTRH2 p.Gln85Ter Likely pathogenic ★ same residue
PTRH2 p.Arg34Ter Likely pathogenic ★ same condition
PTRH2 p.Trp108Ter Pathogenic ★ same condition
PTRH2 p.Trp31Ter Likely pathogenic ★ same condition
PTRH2 p.Val23Ala Likely pathogenic ⚠ same condition
PTRH2 p.Tyr179fs Uncertain significance ★★ same condition
PTRH2 p.Ser43fs Likely pathogenic ★ same condition
PTRH2 p.Val172fs 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/ptrh2-p-gln85pro (accessed [today's date]).

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