Is PARN p.Ser41fs (c.122_123del) pathogenic?

PARN p.Ser41fs (c.122123del) is classified Pathogenic in PARN (ClinVar, Single submitter, 1 submitter; last evaluated 2022-06-18). No gnomAD frequency available for this variant; Associated with dyskeratosis congenita, autosomal recessive 6.

What condition is associated with PARN p.Ser41fs (c.122_123del)?

PARN p.Ser41fs (c.122_123del) is associated with dyskeratosis congenita, autosomal recessive 6, pulmonary fibrosis and/or bone marrow failure, Telomere-related, 4 (ClinVar).

How common is PARN p.Ser41fs (c.122_123del) in the general population?

PARN p.Ser41fs (c.122_123del) is no gnomAD frequency available for this variant (gnomAD).

How is Dyskeratosis congenita inherited?

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

PARN p.Ser41fs

c.122_123del · rs2508640323 · VCV2008012

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

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 3 of 24
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 0.26	phastCons 0.01

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

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: PARN
Protein: p.Ser41fs
Coding: c.122_123del
MANE Select: NM_002582
dbSNP: rs2508640323
Type: Microsatellite
Location: chr16:14628226 (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.Ser41Cys Uncertain significance ★ ⚠ same residue
PARN p.Ser41Phe Uncertain significance ★ ⚠ same residue
PARN p.Glu253fs Pathogenic/Likely pathogenic ★★ same condition
PARN p.Glu139fs Pathogenic ★ same condition
PARN c.659+4_659+7del Conflicting classifications of pathogenicity ★ same condition
PARN p.Asn340del Uncertain significance ★ same condition
PARN p.Glu248del Uncertain significance ★ same condition
PARN p.Lys616dup 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/parn-p-ser41fs (accessed [today's date]).

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