Is MCIDAS p.Pro159Ala (c.475C>G) pathogenic?

MCIDAS p.Pro159Ala (c.475C>G) is classified Uncertain significance in MCIDAS (ClinVar, Single submitter, 1 submitter; last evaluated 2023-10-22). AlphaMissense: likely benign (0.0617); Very rare (popmax 0.00785%, amr); Associated with primary ciliary dyskinesia.

What condition is associated with MCIDAS p.Pro159Ala (c.475C>G)?

MCIDAS p.Pro159Ala (c.475C>G) is associated with primary ciliary dyskinesia (ClinVar).

How common is MCIDAS p.Pro159Ala (c.475C>G) in the general population?

MCIDAS p.Pro159Ala (c.475C>G) is very rare (popmax 0.00785%, 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.Pro159Ala (c.475C>G)?

AlphaMissense predicts likely benign (score 0.0617) — an in-silico prediction, not a clinical call.

MCIDAS p.Pro159Ala

c.475C>G · rs1439093107 · VCV661152

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0617 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00785%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

primary ciliary dyskinesia

Computational evidence

Protein change
AlphaMissense	0.0617	likely benign
REVEL	0.02	moderately benign-leaning
SaProt	LLR -6.65	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 1.2	GERP -2.1, phastCons 0.002
Regional constraint	o/e 0.90	unconstrained · MANE · 6,769 bp · p 0.025 · regional, not allelic
Overall
CADD	7.193	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00785% Admixed American · 4/50,964 alleles

Filtering AF 0.00263% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00153%

Overall 0.00026% 4/1,535,728 alleles · very rare exomes 3/1,383,504 · genomes 1/152,224 · 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.Pro159Ala
Coding: c.475C>G
MANE Select: NM_001190787
dbSNP: rs1439093107
Type: single nucleotide variant
Location: chr5:55222307 (GRCh38)
Gene constraint: LOEUF 0.989 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 61.68 · 1 PDB
Residue 159: 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-pro159ala (accessed [today's date]).

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