Is MLYCD p.Asp148= (c.444C>T) pathogenic?

MLYCD p.Asp148= (c.444C>T) is classified Benign in MLYCD (ClinVar, Multiple submitters, 5 submitters; last evaluated 2026-01-31). Common (popmax 9.8%, afr) — too common for a highly-penetrant pathogenic allele; Associated with malonic aciduria.

What condition is associated with MLYCD p.Asp148= (c.444C>T)?

MLYCD p.Asp148= (c.444C>T) 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.Asp148=

Q: How common is MLYCD p.Asp148= (c.444C>T) in the general population?

MLYCD p.Asp148= (c.444C>T) is common (popmax 9.8%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.444C>T · rs62640904 · VCV95500

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

gnomAD v4.1

Common

common (popmax 9.8%, afr) — 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 0.032	GERP 1.3, phastCons 0.84
Overall
CADD	12.32	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 9.8% African / African-American · 7,293/74,416 alleles

Filtering AF 9.61% ClinGen BA1/BS1 input FAF95, joint · FAF99 9.54%

Overall 1.26% 20,004/1,589,408 alleles · common exomes 14,934/1,437,094 · genomes 5,070/152,314 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	9.8%	10
Ashkenazi Jewishnot grpmax-eligible	2.11%	47
Remaining individualsnot grpmax-eligible	1.47%	68
Finnishnot grpmax-eligible	1.19%	84
Admixed American	1.02%	98
Middle Eastern	0.94%	106
European (non-Finnish)	0.831%	120
South Asian	0.195%	513
East Asian	0.0362%	2,763

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.Asp148=
Coding: c.444C>T
MANE Select: NM_012213
dbSNP: rs62640904
Type: single nucleotide variant
Location: chr16:83899588 (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 148: the 'alpha-helical 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.Asp148Asn Uncertain significance ★ ⚠ same residue
MLYCD p.Asp148fs Likely pathogenic ★ same residue
MLYCD p.Asp148Gly 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

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-asp148 (accessed [today's date]).

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