Is MCEE p.Cys166Ser (c.496T>A) pathogenic?

MCEE p.Cys166Ser (c.496T>A) is classified Uncertain significance in MCEE (ClinVar, Single submitter, 1 submitter; last evaluated 2024-01-22). AlphaMissense: likely pathogenic (0.6052); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with MCEE p.Cys166Ser (c.496T>A)?

MCEE p.Cys166Ser (c.496T>A) is associated with Inborn genetic diseases (ClinVar).

How common is MCEE p.Cys166Ser (c.496T>A) in the general population?

MCEE p.Cys166Ser (c.496T>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about MCEE p.Cys166Ser (c.496T>A)?

AlphaMissense predicts likely pathogenic (score 0.6052) — an in-silico prediction, not a clinical call.

MCEE p.Cys166Ser

c.496T>A · rs1226393266 · VCV3124213

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6052 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.6052	likely pathogenic
REVEL	0.643	indeterminate
SaProt	LLR -11.27	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 11	GERP 1.9, phastCons 1
Regional constraint	o/e 1.01	unconstrained · MANE · 20 kb · p 0.9 · regional, not allelic
Overall
CADD	25.8	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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: MCEE
Protein: p.Cys166Ser
Coding: c.496T>A
MANE Select: NM_032601
dbSNP: rs1226393266
Type: single nucleotide variant
Location: chr2:71110005 (GRCh38)
Gene constraint: LOEUF 0.867 · pLI 0.41 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 87.27 · 2 PDB
Residue 166: the voc domain; an α-helix

Full MCEE 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

MCEE p.Asn115Lys Uncertain significance ★★ ⚠ same condition
MCEE p.Ile159Thr Uncertain significance ★★ ⚠ same condition
MCEE p.Leu79Val Uncertain significance ★★ ⚠ same condition
MCEE p.Ala10Thr Uncertain significance ★ ⚠ same condition
MCEE p.Ala2Val Uncertain significance ★ ⚠ same condition
MCEE p.Ala63Glu Uncertain significance ★ ⚠ same condition
MCEE p.Ala76Thr Uncertain significance ★ ⚠ same condition
MCEE p.Asn115Ser 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/mcee-p-cys166ser (accessed [today's date]).

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