Is PARN p.Leu202= (c.606A>G) pathogenic?

PARN p.Leu202= (c.606A>G) is classified Likely benign in PARN (ClinVar, Single submitter, 1 submitter; last evaluated 2022-09-19). Very rare (popmax 8.68e-05%, nfe); Associated with dyskeratosis congenita, autosomal recessive 6.

What condition is associated with PARN p.Leu202= (c.606A>G)?

PARN p.Leu202= (c.606A>G) is associated with dyskeratosis congenita, autosomal recessive 6, pulmonary fibrosis and/or bone marrow failure, Telomere-related, 4 (ClinVar).

How common is PARN p.Leu202= (c.606A>G) in the general population?

PARN p.Leu202= (c.606A>G) is very rare (popmax 8.68e-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.Leu202=

c.606A>G · rs2508356106 · VCV2413549

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 8.68e-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.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.32	GERP -1.7, phastCons 1
Overall
CADD	8.193	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.68e-05% European (non-Finnish) · 1/1,152,306 alleles

Overall 7.01e-05% 1/1,425,684 alleles · very rare

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.Leu202=
Coding: c.606A>G
MANE Select: NM_002582
dbSNP: rs2508356106
Type: single nucleotide variant
Location: chr16:14609072 (GRCh38)
Gene constraint: LOEUF 0.918 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 81.60 · 3 PDB
Residue 202: the r3h domain

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.Leu202Ile 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
PARN c.962+2T>C Pathogenic/Likely pathogenic ★★ same condition
PARN p.Arg128Ter Pathogenic/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-leu202 (accessed [today's date]).

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