Is MLYCD p.Arg432= (c.1296C>T) pathogenic?

MLYCD p.Arg432= (c.1296C>T) is classified Likely benign in MLYCD (ClinVar, Multiple submitters, 4 submitters; last evaluated 2025-01-20). Ultra-rare (popmax 0.0507%, afr); Associated with malonic aciduria.

What condition is associated with MLYCD p.Arg432= (c.1296C>T)?

MLYCD p.Arg432= (c.1296C>T) is associated with malonic aciduria (ClinVar).

How common is MLYCD p.Arg432= (c.1296C>T) in the general population?

MLYCD p.Arg432= (c.1296C>T) is ultra-rare (popmax 0.0507%, afr) (gnomAD).

How is Malonic aciduria inherited?

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

MLYCD p.Arg432=

c.1296C>T · rs369624204 · VCV2738022

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0507%, afr)

Conditions

malonic aciduria

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 -0.45	GERP -2.8, phastCons 0.02
Overall
CADD	4.842	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0507% African / African-American · 38/74,952 alleles

Filtering AF 0.038% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0334%

Overall 0.00657% 106/1,613,774 alleles · ultra-rare exomes 85/1,461,500 · genomes 21/152,274 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0507%	1,972
European (non-Finnish)	0.00542%	18,435
Remaining individualsnot grpmax-eligible	0.0048%	20,827
Admixed American	0.00167%	60,010

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.Arg432=
Coding: c.1296C>T
MANE Select: NM_012213
dbSNP: rs369624204
Type: single nucleotide variant
Location: chr16:83915303 (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 432: 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.Arg432Cys Uncertain significance ★★ ⚠ same residue
MLYCD p.Arg432His Uncertain significance ★★ ⚠ same residue
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

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-arg432 (accessed [today's date]).

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