Is PARN p.Lys326= (c.978A>G) pathogenic?

PARN p.Lys326= (c.978A>G) is classified Benign/Likely benign in PARN (ClinVar, Multiple submitters, 3 submitters; last evaluated 2026-02-03). Ultra-rare (popmax 0.0503%, mid); Associated with dyskeratosis congenita, autosomal recessive 6.

What condition is associated with PARN p.Lys326= (c.978A>G)?

PARN p.Lys326= (c.978A>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.Lys326= (c.978A>G) in the general population?

PARN p.Lys326= (c.978A>G) is ultra-rare (popmax 0.0503%, mid) (gnomAD).

How is Dyskeratosis congenita inherited?

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

PARN p.Lys326=

c.978A>G · rs200678657 · VCV1164942

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0503%, mid)

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 0.64	GERP -1, phastCons 1
Overall
CADD	10.78	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0503% Middle Eastern · 3/5,960 alleles

Filtering AF 0.0136% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0073%

Overall 0.0153% 239/1,565,652 alleles · ultra-rare exomes 213/1,413,430 · genomes 26/152,222 · joint denominator

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	0.504%	198
Middle Easterngrpmax	0.0503%	1,987
Remaining individualsnot grpmax-eligible	0.0347%	2,885
European (non-Finnish)	0.0062%	16,121
Finnishnot grpmax-eligible	0.00157%	63,788

Ashkenazi Jewish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Lys326=
Coding: c.978A>G
MANE Select: NM_002582
dbSNP: rs200678657
Type: single nucleotide variant
Location: chr16:14584776 (GRCh38)
Gene constraint: LOEUF 0.918 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 81.60 · 3 PDB
Residue 326: an α-helix; a functional site (interaction with poly(a))

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 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
PARN p.Arg237Ter 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-lys326 (accessed [today's date]).

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