Is MCEE p.Val87Ala (c.260T>C) pathogenic?

MCEE p.Val87Ala (c.260T>C) is classified Uncertain significance in MCEE (ClinVar, Single submitter, 1 submitter; last evaluated 2024-12-31). AlphaMissense: likely benign (0.3182); Very rare (popmax 6.19e-05%); Associated with Inborn genetic diseases.

What condition is associated with MCEE p.Val87Ala (c.260T>C)?

MCEE p.Val87Ala (c.260T>C) is associated with Inborn genetic diseases (ClinVar).

How common is MCEE p.Val87Ala (c.260T>C) in the general population?

MCEE p.Val87Ala (c.260T>C) is very rare (popmax 6.19e-05%) (gnomAD).

What do computational predictors say about MCEE p.Val87Ala (c.260T>C)?

AlphaMissense predicts likely benign (score 0.3182) — an in-silico prediction, not a clinical call.

MCEE p.Val87Ala

c.260T>C · VCV3871192

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.3182 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 6.19e-05%)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.3182	likely benign
REVEL	0.358	indeterminate
SaProt	LLR -6.55	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL is indeterminate.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 6.1	GERP -0.62, phastCons 1
Regional constraint	o/e 1.01	unconstrained · MANE · 20 kb · p 0.9 · regional, not allelic
Overall
CADD	24.2	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 6.19e-05%

Overall 6.19e-05% 1/1,614,208 alleles · very rare exomes 1/1,461,870 · genomes 0/152,338 · 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.Val87Ala
Coding: c.260T>C
MANE Select: NM_032601
Type: single nucleotide variant
Location: chr2:71124324 (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 87: a β-strand; the voc domain

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-val87ala (accessed [today's date]).

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