Is PARN p.Gln261= (c.783G>A) pathogenic?

PARN p.Gln261= (c.783G>A) is classified Uncertain significance in PARN (ClinVar, Single submitter, 1 submitter; last evaluated 2022-06-27). Very rare (popmax 8.63e-05%, nfe); Associated with dyskeratosis congenita, autosomal recessive 6.

What condition is associated with PARN p.Gln261= (c.783G>A)?

PARN p.Gln261= (c.783G>A) is associated with dyskeratosis congenita, autosomal recessive 6, pulmonary fibrosis and/or bone marrow failure, Telomere-related, 4 (ClinVar).

How common is PARN p.Gln261= (c.783G>A) in the general population?

PARN p.Gln261= (c.783G>A) is very rare (popmax 8.63e-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.Gln261=

c.783G>A · rs1261797823 · VCV1444079

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 8.63e-05%, nfe)

Conditions

dyskeratosis congenita, autosomal recessive 6

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Splicing
SpliceAI	Δ0.24	donor loss at this position · masked 0 · deltas
Pangolin	Δ0.23	loss · gain 0.07 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 7.6	GERP 1.7, phastCons 1
Overall
CADD	21.6	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.63e-05% European (non-Finnish) · 1/1,158,786 alleles

Overall 6.98e-05% 1/1,432,884 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.Gln261=
Coding: c.783G>A
MANE Select: NM_002582
dbSNP: rs1261797823
Type: single nucleotide variant
Location: chr16:14604146 (GRCh38)
Gene constraint: LOEUF 0.918 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 81.60 · 3 PDB
Residue 261: 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.Gln261Arg Uncertain significance ★ ⚠ same residue
PARN p.Gln261Ter Pathogenic ★ 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

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-gln261 (accessed [today's date]).

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