Is PARN p.Ser309fs (c.925del) pathogenic?

PARN p.Ser309fs (c.925del) is classified Pathogenic in PARN (ClinVar, Single submitter, 1 submitter; last evaluated 2024-10-05). Very rare (popmax 8.89e-05%, nfe); Associated with dyskeratosis congenita, autosomal recessive 6.

What condition is associated with PARN p.Ser309fs (c.925del)?

PARN p.Ser309fs (c.925del) is associated with dyskeratosis congenita, autosomal recessive 6, pulmonary fibrosis and/or bone marrow failure, Telomere-related, 4 (ClinVar).

How common is PARN p.Ser309fs (c.925del) in the general population?

PARN p.Ser309fs (c.925del) is very rare (popmax 8.89e-05%, nfe) (gnomAD).

How is Dyskeratosis congenita inherited?

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

PARN p.Ser309fs

c.925del · VCV3759298

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 8.89e-05%, nfe)

Conditions

dyskeratosis congenita, autosomal recessive 6

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function in a haploinsufficient gene (ClinGen)
NMD	predicted	premature termination codon in exon 14 of 24
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 2.3	GERP 0.24, phastCons 1

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.89e-05% European (non-Finnish) · 1/1,125,338 alleles

Overall 6.53e-05% 1/1,531,472 alleles · very rare exomes 1/1,379,230 · genomes 0/152,242 · 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: PARN
Protein: p.Ser309fs
Coding: c.925del
MANE Select: NM_002582
Type: Deletion
Location: chr16:14586355 (GRCh38)
Gene constraint: LOEUF 0.918 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 81.60 · 3 PDB
Residue 309: an α-helix

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

Disease context

dyskeratosis congenita, autosomal recessive 6 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: pulmonary fibrosis and/or bone marrow failure, Telomere-related, 4

For Dyskeratosis congenita (Orphanet):

Inheritance: Autosomal dominant, Autosomal recessive, X-linked recessive
Onset: Adolescent, Adult, Childhood, Infancy, Neonatal
Prevalence: 1-9 / 1 000 000 (Europe)

Similar variants

PARN p.Ser309= Likely benign ★ same residue
PARN p.Val318fs Pathogenic ★★ same condition
PARN c.840+6del Benign/Likely benign ★★ same condition
PARN c.1263-11_1269del Likely pathogenic ★ same condition
PARN c.1319-2_1319del Likely pathogenic ★ same condition
PARN c.177+1del Pathogenic ★ same condition
PARN c.784-170_840+174del Likely pathogenic ★ same condition
PARN p.Arg237_Tyr238insTer 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-ser309fs (accessed [today's date]).

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