Is MCIDAS p.Ser288Thr (c.862T>A) pathogenic?

MCIDAS p.Ser288Thr (c.862T>A) is classified Uncertain significance in MCIDAS (ClinVar, Single submitter, 1 submitter; last evaluated 2025-12-11). AlphaMissense: likely benign (0.1369); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with MCIDAS p.Ser288Thr (c.862T>A)?

MCIDAS p.Ser288Thr (c.862T>A) is associated with Inborn genetic diseases (ClinVar).

How common is MCIDAS p.Ser288Thr (c.862T>A) in the general population?

MCIDAS p.Ser288Thr (c.862T>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about MCIDAS p.Ser288Thr (c.862T>A)?

AlphaMissense predicts likely benign (score 0.1369) — an in-silico prediction, not a clinical call.

MCIDAS p.Ser288Thr

c.862T>A · VCV4624503

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1369 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1369	likely benign
REVEL	0.083	moderately benign-leaning
SaProt	LLR -7.01	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6.6	GERP 1.5, phastCons 1
Regional constraint	o/e 0.90	unconstrained · MANE · 6,769 bp · p 0.025 · regional, not allelic
Overall
CADD	19.85	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: MCIDAS
Protein: p.Ser288Thr
Coding: c.862T>A
MANE Select: NM_001190787
Type: single nucleotide variant
Location: chr5:55220662 (GRCh38)
Gene constraint: LOEUF 0.989 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 61.68 · 1 PDB
Residue 288: 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

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

MCIDAS p.Ala362Val Uncertain significance ★★ ⚠ same condition
MCIDAS p.Asp141Gly Uncertain significance ★★ ⚠ same condition
MCIDAS p.Pro364Arg Uncertain significance ★★ ⚠ same condition
MCIDAS p.Thr109Met Uncertain significance ★★ ⚠ same condition
MCIDAS p.Thr52Ile Uncertain significance ★★ ⚠ same condition
MCIDAS p.Val122Leu Uncertain significance ★★ ⚠ same condition
MCIDAS p.Ala186Thr Uncertain significance ★ ⚠ same condition
MCIDAS p.Ala273Thr 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-ser288thr (accessed [today's date]).

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