Is LRRC56 p.Pro243= (c.729G>A) pathogenic?

LRRC56 p.Pro243= (c.729G>A) is classified Benign in LRRC56 (ClinVar, Multiple submitters, 6 submitters; last evaluated 2026-02-04). Common (popmax 26.5%, amr) — too common for a highly-penetrant pathogenic allele; Associated with ciliary dyskinesia, primary, 39.

What condition is associated with LRRC56 p.Pro243= (c.729G>A)?

LRRC56 p.Pro243= (c.729G>A) is associated with ciliary dyskinesia, primary, 39 (ClinVar).

How is Primary ciliary dyskinesia inherited?

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

LRRC56 p.Pro243=

Q: How common is LRRC56 p.Pro243= (c.729G>A) in the general population?

LRRC56 p.Pro243= (c.729G>A) is common (popmax 26.5%, amr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.729G>A · rs35537971 · VCV1261003

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

gnomAD v4.1

Common

common (popmax 26.5%, amr) — too common for a highly-penetrant pathogenic allele

Conditions

ciliary dyskinesia, primary, 39

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 4.9	GERP 0.12, phastCons 0.97
Overall
CADD	5.953	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 26.5% Admixed American · 13,423/50,636 alleles

Filtering AF 26.1% ClinGen BA1/BS1 input FAF95, joint · FAF99 26%

Overall 19.2% 297,020/1,544,318 alleles · common exomes 266,649/1,392,362 · genomes 30,371/151,956 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	26.5%	4
African / African-American	22.7%	4
European (non-Finnish)	20.6%	5
Remaining individualsnot grpmax-eligible	18.1%	6
Ashkenazi Jewishnot grpmax-eligible	16.4%	6
Middle Eastern	14.7%	7
Amishnot grpmax-eligible	14.4%	7
Finnishnot grpmax-eligible	13.2%	8
South Asian	8.32%	12
East Asian	1.98%	50

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: LRRC56
Protein: p.Pro243=
Coding: c.729G>A
MANE Select: NM_198075
dbSNP: rs35537971
Type: single nucleotide variant
Location: chr11:551235 (GRCh38)
Gene constraint: LOEUF 1.225 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 56.07
Residue 243: the lrrct domain

Full LRRC56 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

ciliary dyskinesia, primary, 39 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Primary ciliary dyskinesia (Orphanet):

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

Similar variants

LRRC56 p.Tyr53Ter Pathogenic/Likely pathogenic ★★ same condition
LRRC56 p.His324= Uncertain significance ★★ same condition
LRRC56 p.Pro305His Uncertain significance ★★ ⚠ same condition
LRRC56 c.1182-22T>C Benign ★★ same condition
LRRC56 c.423+30C>G Benign ★★ same condition
LRRC56 c.424-9G>A Benign/Likely benign ★★ same condition
LRRC56 c.*23C>G Benign ★★ same condition
LRRC56 p.Arg12Gln Benign ★★ 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/lrrc56-p-pro243 (accessed [today's date]).

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