Is MCEE p.Ala2Val (c.5C>T) pathogenic?

MCEE p.Ala2Val (c.5C>T) is classified Uncertain significance in MCEE (ClinVar, Single submitter, 1 submitter; last evaluated 2024-03-04). AlphaMissense: ambiguous (0.3494); Very rare (popmax 6.22e-05%); Associated with Inborn genetic diseases.

What condition is associated with MCEE p.Ala2Val (c.5C>T)?

MCEE p.Ala2Val (c.5C>T) is associated with Inborn genetic diseases (ClinVar).

How common is MCEE p.Ala2Val (c.5C>T) in the general population?

MCEE p.Ala2Val (c.5C>T) is very rare (popmax 6.22e-05%) (gnomAD).

What do computational predictors say about MCEE p.Ala2Val (c.5C>T)?

AlphaMissense predicts ambiguous (score 0.3494) — an in-silico prediction, not a clinical call.

MCEE p.Ala2Val

c.5C>T · rs367614615 · VCV3124214

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3494 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 6.22e-05%)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense indeterminate

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.3494	ambiguous
REVEL	0.124	moderately benign-leaning
SaProt	LLR -8.80	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.6	GERP 0.78, phastCons 0.9
Regional constraint	o/e 1.01	unconstrained · MANE · 20 kb · p 0.9 · regional, not allelic
Overall
CADD	18.5	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 6.22e-05%

Overall 6.22e-05% 1/1,607,010 alleles · very rare exomes 1/1,454,708 · genomes 0/152,302 · 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: MCEE
Protein: p.Ala2Val
Coding: c.5C>T
MANE Select: NM_032601
dbSNP: rs367614615
Type: single nucleotide variant
Location: chr2:71130215 (GRCh38)
Gene constraint: LOEUF 0.867 · pLI 0.41 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 87.27 · 2 PDB

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.Ala63Glu Uncertain significance ★ ⚠ same condition
MCEE p.Ala76Thr Uncertain significance ★ ⚠ same condition
MCEE p.Asn115Ser Uncertain significance ★ same condition
MCEE p.Cys166Ser 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-ala2val (accessed [today's date]).

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