Is MLYCD p.Leu18= (c.54G>A) pathogenic?

MLYCD p.Leu18= (c.54G>A) is classified Likely benign in MLYCD (ClinVar, Single submitter, 1 submitter; last evaluated 2023-06-05). Ultra-rare (popmax 0.0105%, sas); Associated with malonic aciduria.

What condition is associated with MLYCD p.Leu18= (c.54G>A)?

MLYCD p.Leu18= (c.54G>A) is associated with malonic aciduria (ClinVar).

How common is MLYCD p.Leu18= (c.54G>A) in the general population?

MLYCD p.Leu18= (c.54G>A) is ultra-rare (popmax 0.0105%, sas) (gnomAD).

How is Malonic aciduria inherited?

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

MLYCD p.Leu18=

c.54G>A · rs2151053093 · VCV2825686

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0105%, sas)

Conditions

malonic aciduria

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 -1.2	GERP -2.5
Overall
CADD	0.209	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0105% South Asian · 3/28,658 alleles

Filtering AF 0.00277% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00147%

Overall 0.000255% 3/1,176,908 alleles · ultra-rare exomes 3/1,027,202 · genomes 0/149,706 · 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: MLYCD
Protein: p.Leu18=
Coding: c.54G>A
MANE Select: NM_012213
dbSNP: rs2151053093
Type: single nucleotide variant
Location: chr16:83899198 (GRCh38)
Gene constraint: LOEUF 1.165 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 90.16 · 2 PDB

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-leu18 (accessed [today's date]).

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