Is MCIDAS p.Pro44Gln (c.131C>A) pathogenic?

MCIDAS p.Pro44Gln (c.131C>A) is classified Uncertain significance in MCIDAS (ClinVar, Single submitter, 1 submitter; last evaluated 2020-09-21). AlphaMissense: likely benign (0.1143); Very rare (popmax 0.000455%, nfe).

How common is MCIDAS p.Pro44Gln (c.131C>A) in the general population?

MCIDAS p.Pro44Gln (c.131C>A) is very rare (popmax 0.000455%, nfe) (gnomAD).

What do computational predictors say about MCIDAS p.Pro44Gln (c.131C>A)?

AlphaMissense predicts likely benign (score 0.1143) — an in-silico prediction, not a clinical call.

MCIDAS p.Pro44Gln

c.131C>A · VCV4970384

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1143 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000455%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1143	likely benign
REVEL	0.108	moderately benign-leaning
SaProt	LLR -6.74	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 4.7	GERP 1.5, phastCons 1
Regional constraint	o/e 0.90	unconstrained · MANE · 6,769 bp · p 0.025 · regional, not allelic
Overall
CADD	23.8	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 0.000455% European (non-Finnish) · 5/1,099,982 alleles

Filtering AF 0.000133% ClinGen BA1/BS1 input FAF95, joint · FAF99 9.7e-05%

Overall 0.000349% 5/1,432,202 alleles · very rare exomes 5/1,279,852 · genomes 0/152,350 · 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.Pro44Gln
Coding: c.131C>A
MANE Select: NM_001190787
Type: single nucleotide variant
Location: chr5:55226921 (GRCh38)
Gene constraint: LOEUF 0.989 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 61.68 · 1 PDB
Residue 44: the 'necessary and sufficient for its degradation during the cell cycle' region

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

Similar variants

MCIDAS p.Leu335Ter Pathogenic/Likely pathogenic ★★ same type
MCIDAS p.Ala228Ser Uncertain significance ★★ ⚠ same type
MCIDAS p.Ala362Val Uncertain significance ★★ ⚠ same type
MCIDAS p.Ala93Pro Uncertain significance ★★ ⚠ same type
MCIDAS p.Arg285Thr Uncertain significance ★★ ⚠ same type
MCIDAS p.Asp141Gly Uncertain significance ★★ ⚠ same type
MCIDAS p.Ile77Val Uncertain significance ★★ ⚠ same type
MCIDAS p.Pro364Arg Uncertain significance ★★ ⚠ same type

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-pro44gln (accessed [today's date]).

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