Is MCIDAS p.Arg230= (c.690A>C) pathogenic?

MCIDAS p.Arg230= (c.690A>C) is classified Likely benign in MCIDAS (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-05-22). Very rare (popmax 0.0014%, nfe); Associated with primary ciliary dyskinesia.

What condition is associated with MCIDAS p.Arg230= (c.690A>C)?

MCIDAS p.Arg230= (c.690A>C) is associated with primary ciliary dyskinesia (ClinVar).

How common is MCIDAS p.Arg230= (c.690A>C) in the general population?

MCIDAS p.Arg230= (c.690A>C) is very rare (popmax 0.0014%, nfe) (gnomAD).

How is Primary ciliary dyskinesia inherited?

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

MCIDAS p.Arg230=

c.690A>C · rs1215757911 · VCV1963518

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.0014%, nfe)

Conditions

primary ciliary dyskinesia

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 0.39	GERP -2.4, phastCons 0.99
Overall
CADD	13.67	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0014% European (non-Finnish) · 16/1,146,886 alleles

Filtering AF 0.000826% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000668%

Overall 0.00104% 16/1,535,972 alleles · very rare exomes 15/1,383,772 · genomes 1/152,200 · joint denominator

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: MCIDAS
Protein: p.Arg230=
Coding: c.690A>C
MANE Select: NM_001190787
dbSNP: rs1215757911
Type: single nucleotide variant
Location: chr5:55221043 (GRCh38)
Gene constraint: LOEUF 0.989 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 61.68 · 1 PDB
Residue 230: an α-helix; the 'necessary and sufficient for proper nuclear localization' region; the 'necessary and sufficient for interaction with gmnn and sufficient for homodimerization' region; a UniProt-annotated variant site (in cild42; reduced number of cilia and basal bodies)

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

Disease context

primary ciliary dyskinesia — 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

MCIDAS p.Leu335Ter Pathogenic/Likely pathogenic ★★ same condition
MCIDAS p.Ala228Ser Uncertain significance ★★ ⚠ same condition
MCIDAS p.Ala362Val Uncertain significance ★★ ⚠ same condition
MCIDAS p.Ala93Pro Uncertain significance ★★ ⚠ same condition
MCIDAS p.Arg285Thr Uncertain significance ★★ ⚠ same condition
MCIDAS p.Asp141Gly Uncertain significance ★★ ⚠ same condition
MCIDAS p.Pro364Arg Uncertain significance ★★ ⚠ same condition
MCIDAS p.Ser347Phe Uncertain significance ★★ ⚠ 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/mcidas-p-arg230 (accessed [today's date]).

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