Is PARN p.Ala156Ser (c.466G>T) pathogenic?

PARN p.Ala156Ser (c.466G>T) is classified Conflicting classifications of pathogenicity in PARN (ClinVar, Conflicting submitters, 7 submitters; last evaluated 2026-05-01). AlphaMissense: likely benign (0.0808); Ultra-rare (popmax 0.0333%, nfe); Associated with primary ciliary dyskinesia 20.

How common is PARN p.Ala156Ser (c.466G>T) in the general population?

PARN p.Ala156Ser (c.466G>T) is ultra-rare (popmax 0.0333%, nfe) (gnomAD).

How is Primary ciliary dyskinesia inherited?

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

What do computational predictors say about PARN p.Ala156Ser (c.466G>T)?

AlphaMissense predicts likely benign (score 0.0808) — an in-silico prediction, not a clinical call.

PARN p.Ala156Ser

Q: What condition is associated with PARN p.Ala156Ser (c.466G>T)?

PARN p.Ala156Ser (c.466G>T) is associated with primary ciliary dyskinesia 20, dyskeratosis congenita, autosomal recessive 6, pulmonary fibrosis and/or bone marrow failure, Telomere-related, 4 (ClinVar).

c.466G>T · rs200103366 · VCV569031

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 7 submitters

AlphaMissense

likely benign

0.0808 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0333%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

primary ciliary dyskinesia 20

Computational evidence

Protein change
AlphaMissense	0.0808	likely benign
REVEL	0.217	benign-leaning
SaProt	LLR -5.09	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.82	GERP 0.8, phastCons 0.24
Regional constraint	o/e 1.03	unconstrained · MANE · 193 kb · p 0.44 · regional, not allelic
Overall
CADD	17.7	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0333% European (non-Finnish) · 390/1,171,348 alleles

Filtering AF 0.0305% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0295%

Overall 0.027% 433/1,604,418 alleles · ultra-rare exomes 378/1,452,246 · genomes 55/152,172 · joint denominator

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	0.0422%	2,370
European (non-Finnish)grpmax	0.0333%	3,003
Remaining individualsnot grpmax-eligible	0.0145%	6,901
African / African-American	0.00937%	10,674

Finnish 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.Ala156Ser
Coding: c.466G>T
MANE Select: NM_002582
dbSNP: rs200103366
Type: single nucleotide variant
Location: chr16:14610732 (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

primary ciliary dyskinesia 20 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: dyskeratosis congenita, autosomal recessive 6 pulmonary fibrosis and/or bone marrow failure, Telomere-related, 4

For Primary ciliary dyskinesia (Orphanet):

Inheritance: Autosomal dominant, Autosomal recessive, X-linked recessive
Onset: Neonatal
Prevalence: 1-5 / 10 000 (Pakistan)

Similar variants

PARN p.Ala156Thr Uncertain significance ★ ⚠ same residue
PARN p.Ala156Val Uncertain significance ★ ⚠ same residue
PARN p.Ala156= Likely benign ★ 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

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-ala156ser (accessed [today's date]).

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