Is MCEE p.Pro34= (c.102C>G) pathogenic?

MCEE p.Pro34= (c.102C>G) is classified Conflicting classifications of pathogenicity in MCEE (ClinVar, Conflicting submitters, 6 submitters; last evaluated 2026-02-01). Rare (popmax 0.738%, nfe); Associated with methylmalonic acidemia due to methylmalonyl-CoA epimerase deficiency.

What condition is associated with MCEE p.Pro34= (c.102C>G)?

MCEE p.Pro34= (c.102C>G) is associated with methylmalonic acidemia due to methylmalonyl-CoA epimerase deficiency (ClinVar).

How common is MCEE p.Pro34= (c.102C>G) in the general population?

MCEE p.Pro34= (c.102C>G) is rare (popmax 0.738%, nfe) (gnomAD).

MCEE p.Pro34=

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.102C>G · rs146573280 · VCV195391

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 6 submitters

gnomAD v4.1

Rare

rare (popmax 0.738%, nfe)

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	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 0.33	GERP -3.2
Overall
CADD	4.343	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.738% European (non-Finnish) · 8,705/1,180,032 alleles

Filtering AF 0.725% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.719%

Overall 0.679% 10,953/1,614,128 alleles · rare exomes 10,022/1,461,830 · genomes 931/152,298 · joint denominator

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	1.78%	56
European (non-Finnish)grpmax	0.738%	136
Remaining individualsnot grpmax-eligible	0.707%	141
Admixed American	0.673%	149
South Asian	0.153%	655
Ashkenazi Jewishnot grpmax-eligible	0.118%	846
African / African-American	0.113%	883
Middle Eastern	0.066%	1,516
East Asian	0.00223%	44,892

Finnish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Pro34=
Coding: c.102C>G
MANE Select: NM_032601
dbSNP: rs146573280
Type: single nucleotide variant
Location: chr2:71124482 (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

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 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
MCEE p.Met1Ile 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-pro34 (accessed [today's date]).

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