Is MLYCD p.Ser191fs (c.570_571dup) pathogenic?

MLYCD p.Ser191fs (c.570571dup) is classified Pathogenic in MLYCD (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-22). Very rare (popmax 0.00167%, amr); Associated with malonic aciduria.

What condition is associated with MLYCD p.Ser191fs (c.570_571dup)?

MLYCD p.Ser191fs (c.570_571dup) is associated with malonic aciduria (ClinVar).

How common is MLYCD p.Ser191fs (c.570_571dup) in the general population?

MLYCD p.Ser191fs (c.570_571dup) is very rare (popmax 0.00167%, amr) (gnomAD).

How is Malonic aciduria inherited?

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

MLYCD p.Ser191fs

c.570_571dup · VCV4694288

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00167%, amr)

Conditions

malonic aciduria

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 2 of 5
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 12	GERP 1.5, phastCons 1
Overall
CADD	33.0	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00167% Admixed American · 1/60,024 alleles

Filtering AF 7.9e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 5.4e-05%

Overall 0.00031% 5/1,614,094 alleles · very rare exomes 3/1,461,876 · genomes 2/152,218 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00167%	60,024
European (non-Finnish)	0.000339%	295,004

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.Ser191fs
Coding: c.570_571dup
MANE Select: NM_012213
Type: Duplication
Location: chr16:83907025 (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 191: 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.Ser191= Likely benign ★ same residue
MLYCD p.Gln124fs Pathogenic ★ same condition
MLYCD p.Gln266fs Pathogenic ★ same condition
MLYCD p.Leu401fs Likely pathogenic ★ same condition
MLYCD p.Val252fs Pathogenic ★ same condition
MLYCD p.Ter494TrpextTer? Uncertain significance ★ same condition
MLYCD c.641+10dup Likely benign ★ same condition
MLYCD p.Arg21fs Pathogenic/Likely pathogenic ★★ 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-ser191fs (accessed [today's date]).

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