Is MLYCD p.Glu348Asp (c.1044G>T) pathogenic?

MLYCD p.Glu348Asp (c.1044G>T) is classified Conflicting classifications of pathogenicity in MLYCD (ClinVar, Conflicting submitters, 8 submitters; last evaluated 2026-01-28). AlphaMissense: likely benign (0.0701); Rare (popmax 0.188%, nfe); Associated with malonic aciduria.

What condition is associated with MLYCD p.Glu348Asp (c.1044G>T)?

MLYCD p.Glu348Asp (c.1044G>T) is associated with malonic aciduria (ClinVar).

How common is MLYCD p.Glu348Asp (c.1044G>T) in the general population?

MLYCD p.Glu348Asp (c.1044G>T) is rare (popmax 0.188%, nfe) (gnomAD).

How is Malonic aciduria inherited?

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

What do computational predictors say about MLYCD p.Glu348Asp (c.1044G>T)?

AlphaMissense predicts likely benign (score 0.0701) — an in-silico prediction, not a clinical call.

MLYCD p.Glu348Asp

c.1044G>T · rs138675420 · VCV320731

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 8 submitters

AlphaMissense

likely benign

0.0701 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.188%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

malonic aciduria

Computational evidence

Protein change
AlphaMissense	0.0701	likely benign
REVEL	0.21	benign-leaning
SaProt	LLR -6.47	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -2.3	GERP -2.8
Regional constraint	o/e 1.38	unconstrained · MANE · 16 kb · p 1.5e-22 · regional, not allelic
Overall
CADD	0.074	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 0.188% European (non-Finnish) · 2,224/1,180,050 alleles

Filtering AF 0.182% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.179%

Overall 0.149% 2,403/1,614,250 alleles · rare exomes 2,234/1,461,892 · genomes 169/152,358 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.188%	531
Finnishnot grpmax-eligible	0.116%	866
Remaining individualsnot grpmax-eligible	0.104%	962
African / African-American	0.032%	3,128
Admixed American	0.0267%	3,752

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: MLYCD
Protein: p.Glu348Asp
Coding: c.1044G>T
MANE Select: NM_012213
dbSNP: rs138675420
Type: single nucleotide variant
Location: chr16:83915051 (GRCh38)
Gene constraint: LOEUF 1.165 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 90.16 · 2 PDB
Residue 348: the 'catalytic domain' region; a β-strand

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

Disease context

malonic aciduria — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Malonic aciduria (Orphanet):

Inheritance: Autosomal recessive
Onset: Childhood

Similar variants

MLYCD p.Ser187Ter Pathogenic ★★ same condition
MLYCD c.*218C>A Uncertain significance ★★ same condition
MLYCD p.Ala119Ser Uncertain significance ★★ ⚠ same condition
MLYCD p.Ala415Thr Uncertain significance ★★ ⚠ same condition
MLYCD p.Arg199Gln Uncertain significance ★★ ⚠ same condition
MLYCD p.Arg235Gly Uncertain significance ★★ ⚠ same condition
MLYCD p.Arg392Gln Uncertain significance ★★ ⚠ same condition
MLYCD p.Arg392Trp 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/mlycd-p-glu348asp (accessed [today's date]).

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