Is MLYCD p.Tyr131= (c.393C>T) pathogenic?

MLYCD p.Tyr131= (c.393C>T) is classified Benign/Likely benign in MLYCD (ClinVar, Multiple submitters, 5 submitters; last evaluated 2026-02-01). Rare (popmax 0.517%, sas); Associated with malonic aciduria.

What condition is associated with MLYCD p.Tyr131= (c.393C>T)?

MLYCD p.Tyr131= (c.393C>T) is associated with malonic aciduria (ClinVar).

How common is MLYCD p.Tyr131= (c.393C>T) in the general population?

MLYCD p.Tyr131= (c.393C>T) is rare (popmax 0.517%, sas) (gnomAD).

How is Malonic aciduria inherited?

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

MLYCD p.Tyr131=

c.393C>T · rs560831102 · VCV390554

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

gnomAD v4.1

Rare

rare (popmax 0.517%, 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 -0.022	GERP 0.17, phastCons 0.83
Overall
CADD	11.38	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.517% South Asian · 468/90,436 alleles

Filtering AF 0.479% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.463%

Overall 0.0401% 638/1,591,090 alleles · rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.517%	193
Middle Eastern	0.172%	582
Ashkenazi Jewishnot grpmax-eligible	0.106%	946
Remaining individualsnot grpmax-eligible	0.0485%	2,062
Admixed American	0.0218%	4,589
European (non-Finnish)	0.00714%	14,011
Finnishnot grpmax-eligible	0.00209%	47,848
African / African-American	0.00135%	74,074

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.Tyr131=
Coding: c.393C>T
MANE Select: NM_012213
dbSNP: rs560831102
Type: single nucleotide variant
Location: chr16:83899537 (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 131: the 'alpha-helical domain' region; an α-helix

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-tyr131 (accessed [today's date]).

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