Is PARN p.Phe355fs (c.1064del) pathogenic?

PARN p.Phe355fs (c.1064del) is classified Pathogenic in PARN (ClinVar, Single submitter, 1 submitter; last evaluated 2024-04-16). Associated with dyskeratosis congenita, autosomal recessive 6.

What condition is associated with PARN p.Phe355fs (c.1064del)?

PARN p.Phe355fs (c.1064del) is associated with dyskeratosis congenita, autosomal recessive 6, pulmonary fibrosis and/or bone marrow failure, Telomere-related, 4 (ClinVar).

How is Dyskeratosis congenita inherited?

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

PARN p.Phe355fs

c.1064del · VCV3755898

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

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 16 of 24
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 4.4	GERP 1.6, phastCons 1

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

Variant & gene context

Gene: PARN
Protein: p.Phe355fs
Coding: c.1064del
MANE Select: NM_002582
Type: Deletion
Location: chr16:14584364 (GRCh38)
Gene constraint: LOEUF 0.918 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 81.60 · 3 PDB

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.Phe355Ser Uncertain significance ★ ⚠ 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-phe355fs (accessed [today's date]).

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