Is MCEE p.Val127= (c.381G>C) pathogenic?

MCEE p.Val127= (c.381G>C) is classified Likely benign in MCEE (ClinVar, Single submitter, 1 submitter; last evaluated 2025-10-06). Absent from gnomAD v4.1; Associated with methylmalonic acidemia due to methylmalonyl-CoA epimerase deficiency.

What condition is associated with MCEE p.Val127= (c.381G>C)?

MCEE p.Val127= (c.381G>C) is associated with methylmalonic acidemia due to methylmalonyl-CoA epimerase deficiency (ClinVar).

How common is MCEE p.Val127= (c.381G>C) in the general population?

MCEE p.Val127= (c.381G>C) is absent from gnomAD v4.1 (gnomAD).

MCEE p.Val127=

Q: How is Methylmalonic acidemia due to methylmalonyl-CoA epimerase deficiency inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

c.381G>C · rs1327966561 · VCV1082651

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

methylmalonic acidemia due to methylmalonyl-CoA epimerase deficiency

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>T here scores Δ0.83 · evaluated, not missing
Constraint at this position
Conservation	phyloP 3.1	GERP 0.7, phastCons 1
Overall
CADD	11.47	PHRED · no single calibrated threshold — expert panels disagree

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.Val127=
Coding: c.381G>C
MANE Select: NM_032601
dbSNP: rs1327966561
Type: single nucleotide variant
Location: chr2:71110120 (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 127: the voc domain; a β-strand

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

Disease context

methylmalonic acidemia due to methylmalonyl-CoA epimerase deficiency — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Methylmalonic acidemia due to methylmalonyl-CoA epimerase deficiency (Orphanet):

Inheritance: Autosomal recessive
Onset: Childhood, Infancy

Similar variants

MCEE p.Val127Met Uncertain significance ★ ⚠ same residue
MCEE c.379-644A>G Likely pathogenic ★★ same condition
MCEE p.Arg47Ter Pathogenic ★★ same condition
MCEE p.Arg47Leu Uncertain significance ★★ ⚠ same condition
MCEE p.Asn115Lys Uncertain significance ★★ ⚠ same condition
MCEE p.Glu174Gln Uncertain significance ★★ same condition
MCEE p.Ile159Thr Uncertain significance ★★ ⚠ same condition
MCEE p.Leu79Val 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-val127 (accessed [today's date]).

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