Is MLYCD p.Arg12fs (c.22_34dup) pathogenic?

MLYCD p.Arg12fs (c.2234dup) is classified Pathogenic in MLYCD (ClinVar, Single submitter, 1 submitter; last evaluated 2023-11-05). Ultra-rare (popmax 0.0148%, afr); Associated with malonic aciduria.

What condition is associated with MLYCD p.Arg12fs (c.22_34dup)?

MLYCD p.Arg12fs (c.22_34dup) is associated with malonic aciduria (ClinVar).

How common is MLYCD p.Arg12fs (c.22_34dup) in the general population?

MLYCD p.Arg12fs (c.22_34dup) is ultra-rare (popmax 0.0148%, afr) (gnomAD).

How is Malonic aciduria inherited?

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

MLYCD p.Arg12fs

c.22_34dup · rs938617354 · VCV1400055

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

ultra-rare (popmax 0.0148%, afr)

Conditions

malonic aciduria

⚠ Built without this gene's context — gene constraint and dosage, protein structure, pathways, panels and related-variant links were not looked up for this page. why

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function; NMD-escape possible for C-terminal truncations
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP -1.3	GERP -0.95
Overall
CADD	27.1	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 0.0148% African / African-American · 9/60,814 alleles

Filtering AF 0.00764% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00572%

Overall 0.00087% 10/1,148,992 alleles · ultra-rare exomes 5/999,224 · genomes 5/149,768 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0148%	6,757
East Asian	0.00506%	19,780

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.Arg12fs
Coding: c.22_34dup
MANE Select: NM_012213
dbSNP: rs938617354
Type: Duplication
Location: chr16:83899157 (GRCh38)

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

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-arg12fs (accessed [today's date]).

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