Is PARN p.Arg237Ter (c.709C>T) pathogenic?

PARN p.Arg237Ter (c.709C>T) is classified Pathogenic/Likely pathogenic in PARN (ClinVar, Multiple submitters, 4 submitters; last evaluated 2024-02-22). Very rare (popmax 0.00114%, sas); Associated with PARN-related disorder.

How common is PARN p.Arg237Ter (c.709C>T) in the general population?

PARN p.Arg237Ter (c.709C>T) is very rare (popmax 0.00114%, sas) (gnomAD).

PARN p.Arg237Ter

Q: What condition is associated with PARN p.Arg237Ter (c.709C>T)?

PARN p.Arg237Ter (c.709C>T) is associated with PARN-related disorder, dyskeratosis congenita, autosomal recessive 6, pulmonary fibrosis and/or bone marrow failure, Telomere-related, 4 (ClinVar).

c.709C>T · rs760506977 · VCV933700

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00114%, sas)

Conditions

PARN-related disorder

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 in a haploinsufficient gene (ClinGen)
NMD	predicted	premature termination codon in exon 11 of 24
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.5	GERP 0.91, phastCons 1
Overall
CADD	39.0	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 0.00114% South Asian · 1/87,466 alleles

Filtering AF 0.000298% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000216%

Overall 0.000571% 9/1,575,604 alleles · very rare exomes 9/1,423,748 · genomes 0/151,856 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00114%	87,466
European (non-Finnish)	0.000694%	144,169

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: PARN
Protein: p.Arg237Ter
Coding: c.709C>T
MANE Select: NM_002582
dbSNP: rs760506977
Type: single nucleotide variant
Location: chr16:14604220 (GRCh38)
Gene constraint: LOEUF 0.918 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 81.60 · 3 PDB
Residue 237: the r3h domain; a β-strand

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

Disease context

PARN-related disorder

Also linked: dyskeratosis congenita, autosomal recessive 6 pulmonary fibrosis and/or bone marrow failure, Telomere-related, 4

Similar variants

PARN p.Arg237Gln Uncertain significance ★★ ⚠ same residue
PARN p.Arg237_Tyr238insTer Pathogenic ★ same residue
PARN p.Arg237Leu Uncertain significance ★ ⚠ same residue
PARN c.1006-2A>G Pathogenic/Likely pathogenic ★★ same condition
PARN c.1405+1G>T Likely pathogenic ★★ same condition
PARN c.1481-1G>A Pathogenic/Likely pathogenic ★★ same condition
PARN c.178-1G>C Likely pathogenic ★★ same condition
PARN c.784-1G>A 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/parn-p-arg237ter (accessed [today's date]).

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