Is PTRH2 p.Arg34Ter (c.100C>T) pathogenic?

PTRH2 p.Arg34Ter (c.100C>T) is classified Likely pathogenic in PTRH2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-03-16). Very rare (popmax 0.00133%, afr); Associated with neurologic, endocrine, and pancreatic disease, multisystem, infantile-onset 1.

What condition is associated with PTRH2 p.Arg34Ter (c.100C>T)?

PTRH2 p.Arg34Ter (c.100C>T) is associated with neurologic, endocrine, and pancreatic disease, multisystem, infantile-onset 1 (ClinVar).

How common is PTRH2 p.Arg34Ter (c.100C>T) in the general population?

PTRH2 p.Arg34Ter (c.100C>T) is very rare (popmax 0.00133%, afr) (gnomAD).

PTRH2 p.Arg34Ter

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.100C>T · VCV4814177

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00133%, afr)

Conditions

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

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function
NMD	escapes	premature termination codon in the last exon (2 of 2) — the truncated protein is likely expressed. PVS1 input, not an applied code
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.9	GERP -0.1, phastCons 1
Overall
CADD	36.0	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00133% African / African-American · 1/75,026 alleles

Filtering AF 0.000763% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000605%

Overall 0.000991% 16/1,614,080 alleles · very rare exomes 16/1,461,850 · genomes 0/152,230 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00133%	75,026
European (non-Finnish)	0.00127%	78,668

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: PTRH2
Protein: p.Arg34Ter
Coding: c.100C>T
MANE Select: NM_016077
Type: single nucleotide variant
Location: chr17:59697879 (GRCh38)
Gene constraint: LOEUF 1.322 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 84.10 · 1 PDB

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

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

Inheritance: Autosomal recessive
Onset: Infancy

Similar variants

PTRH2 p.Arg34Gln Uncertain significance ★ ⚠ same residue
PTRH2 p.Gln85Pro Pathogenic ★★ same condition
PTRH2 p.Trp108Ter Pathogenic ★ same condition
PTRH2 p.Trp31Ter 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
PTRH2 c.1-124A>G Likely benign ★★ same type

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-arg34ter (accessed [today's date]).

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