Is MCIDAS p.Pro384His (c.1151C>A) pathogenic?

MCIDAS p.Pro384His (c.1151C>A) is classified Likely pathogenic in MCIDAS (ClinVar, Single submitter, 1 submitter; last evaluated 2025-09-15). AlphaMissense: likely pathogenic (0.9569); Very rare (popmax 0.00392%, amr); Associated with primary ciliary dyskinesia.

What condition is associated with MCIDAS p.Pro384His (c.1151C>A)?

MCIDAS p.Pro384His (c.1151C>A) is associated with primary ciliary dyskinesia (ClinVar).

How common is MCIDAS p.Pro384His (c.1151C>A) in the general population?

MCIDAS p.Pro384His (c.1151C>A) is very rare (popmax 0.00392%, amr) (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 MCIDAS p.Pro384His (c.1151C>A)?

AlphaMissense predicts likely pathogenic (score 0.9569) — an in-silico prediction, not a clinical call.

MCIDAS p.Pro384His

c.1151C>A · rs939457499 · VCV1502494

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9569 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00392%, amr)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

primary ciliary dyskinesia

Computational evidence

Protein change
AlphaMissense	0.9569	likely pathogenic ✓ concordant with ClinVar · top 3% in MCIDAS
REVEL	0.394	indeterminate
SaProt	LLR -13.12	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 1.5, phastCons 1
Regional constraint	o/e 0.90	unconstrained · MANE · 6,769 bp · p 0.025 · regional, not allelic
Overall
CADD	28.9	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 0.00392% Admixed American · 2/50,972 alleles

Filtering AF 0.000651% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000243%

Overall 0.00013% 2/1,534,422 alleles · very rare exomes 2/1,382,096 · genomes 0/152,326 · 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.Pro384His
Coding: c.1151C>A
MANE Select: NM_001190787
dbSNP: rs939457499
Type: single nucleotide variant
Location: chr5:55220373 (GRCh38)
Gene constraint: LOEUF 0.989 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 61.68 · 1 PDB
Residue 384: the 'necessary and sufficient for proper nuclear localization' 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-pro384his (accessed [today's date]).

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