Is MCEE p.Lys60= (c.180G>A) pathogenic?

MCEE p.Lys60= (c.180G>A) is classified Likely benign in MCEE (ClinVar, Single submitter, 1 submitter; last evaluated 2024-11-23). Ultra-rare (popmax 0.0667%, amr); Associated with methylmalonic acidemia due to methylmalonyl-CoA epimerase deficiency.

What condition is associated with MCEE p.Lys60= (c.180G>A)?

MCEE p.Lys60= (c.180G>A) is associated with methylmalonic acidemia due to methylmalonyl-CoA epimerase deficiency (ClinVar).

How common is MCEE p.Lys60= (c.180G>A) in the general population?

MCEE p.Lys60= (c.180G>A) is ultra-rare (popmax 0.0667%, amr) (gnomAD).

MCEE p.Lys60=

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.180G>A · rs778261717 · VCV792271

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0667%, amr)

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	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.096	GERP 0.69, phastCons 0.27
Overall
CADD	7.096	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0667% Admixed American · 40/59,988 alleles

Filtering AF 0.0503% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0446%

Overall 0.00316% 51/1,613,990 alleles · ultra-rare exomes 28/1,461,876 · genomes 23/152,114 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0667%	1,500
South Asian	0.011%	9,109
Remaining individualsnot grpmax-eligible	0.0016%	62,484

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.Lys60=
Coding: c.180G>A
MANE Select: NM_032601
dbSNP: rs778261717
Type: single nucleotide variant
Location: chr2:71124404 (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 60: an α-helix; the voc domain

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.Lys60Gln Conflicting classifications of pathogenicity ★ ⚠ 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-lys60 (accessed [today's date]).

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