Is MLYCD p.Ser244= (c.732G>A) pathogenic?

MLYCD p.Ser244= (c.732G>A) is classified Benign in MLYCD (ClinVar, Multiple submitters, 5 submitters; last evaluated 2026-02-04). Common (popmax 13.7%, eas) — too common for a highly-penetrant pathogenic allele; Associated with malonic aciduria.

What condition is associated with MLYCD p.Ser244= (c.732G>A)?

MLYCD p.Ser244= (c.732G>A) is associated with malonic aciduria (ClinVar).

How is Malonic aciduria inherited?

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

MLYCD p.Ser244=

Q: How common is MLYCD p.Ser244= (c.732G>A) in the general population?

MLYCD p.Ser244= (c.732G>A) is common (popmax 13.7%, eas) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.732G>A · rs2278038 · VCV138235

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

gnomAD v4.1

Common

common (popmax 13.7%, eas) — too common for a highly-penetrant pathogenic allele

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 -9.8	GERP -3.1
Overall
CADD	0.033	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 13.7% East Asian · 6,169/44,868 alleles

Filtering AF 13.5% ClinGen BA1/BS1 input FAF95, joint · FAF99 13.3%

Overall 5.05% 81,531/1,614,072 alleles · common

Ancestry group	Frequency	1 in
East Asiangrpmax	13.7%	7
Admixed American	11.6%	9
Amishnot grpmax-eligible	6.58%	15
Finnishnot grpmax-eligible	6.51%	15
European (non-Finnish)	4.99%	20
Remaining individualsnot grpmax-eligible	4.42%	23
South Asian	1.81%	55
Middle Eastern	0.99%	101
African / African-American	0.884%	113
Ashkenazi Jewishnot grpmax-eligible	0.49%	204

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.Ser244=
Coding: c.732G>A
MANE Select: NM_012213
dbSNP: rs2278038
Type: single nucleotide variant
Location: chr16:83908216 (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 244: the 'catalytic domain' region

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.Ser244Leu 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
MLYCD p.Arg392Gln 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-ser244 (accessed [today's date]).

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