Is MCIDAS p.Ala93Pro (c.277G>C) pathogenic?

MCIDAS p.Ala93Pro (c.277G>C) is classified Uncertain significance in MCIDAS (ClinVar, Multiple submitters, 2 submitters; last evaluated 2017-01-05). AlphaMissense: likely benign (0.0911); Very rare (popmax 0.00402%, nfe); Associated with primary ciliary dyskinesia.

What condition is associated with MCIDAS p.Ala93Pro (c.277G>C)?

MCIDAS p.Ala93Pro (c.277G>C) is associated with primary ciliary dyskinesia (ClinVar).

How common is MCIDAS p.Ala93Pro (c.277G>C) in the general population?

MCIDAS p.Ala93Pro (c.277G>C) is very rare (popmax 0.00402%, 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 MCIDAS p.Ala93Pro (c.277G>C)?

AlphaMissense predicts likely benign (score 0.0911) — an in-silico prediction, not a clinical call.

MCIDAS p.Ala93Pro

c.277G>C · rs115971569 · VCV454528

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0911 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00402%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

primary ciliary dyskinesia

Computational evidence

Protein change
AlphaMissense	0.0911	likely benign
REVEL	0.053	moderately benign-leaning
SaProt	LLR -5.88	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 0.59	GERP -0.11, phastCons 1
Regional constraint	o/e 0.90	unconstrained · MANE · 6,769 bp · p 0.025 · regional, not allelic
Overall
CADD	18.29	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 0.00402% European (non-Finnish) · 46/1,145,284 alleles

Filtering AF 0.00308% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00275%

Overall 0.00307% 47/1,532,396 alleles · very rare exomes 46/1,380,060 · genomes 1/152,336 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00402%	24,897
Remaining individualsnot grpmax-eligible	0.00167%	59,824

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.Ala93Pro
Coding: c.277G>C
MANE Select: NM_001190787
dbSNP: rs115971569
Type: single nucleotide variant
Location: chr5:55226608 (GRCh38)
Gene constraint: LOEUF 0.989 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 61.68 · 1 PDB
Residue 93: the 'necessary and sufficient for its degradation during the cell cycle' region; the 'disordered' region

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.Ala93Thr Uncertain significance ★ ⚠ same residue
MCIDAS p.Ala93Ser Uncertain significance ★ ⚠ same residue
MCIDAS p.Leu335Ter Pathogenic/Likely pathogenic ★★ same condition
MCIDAS p.Ala228Ser Uncertain significance ★★ ⚠ same condition
MCIDAS p.Ala362Val 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

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-ala93pro (accessed [today's date]).

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