Is MLYCD p.Leu8fs (c.22_34del) pathogenic?

MLYCD p.Leu8fs (c.2234del) is classified Pathogenic in MLYCD (ClinVar, Single submitter, 1 submitter; last evaluated 2023-09-19). Very rare (popmax 0.000426%, nfe); Associated with malonic aciduria.

What condition is associated with MLYCD p.Leu8fs (c.22_34del)?

MLYCD p.Leu8fs (c.22_34del) is associated with malonic aciduria (ClinVar).

How common is MLYCD p.Leu8fs (c.22_34del) in the general population?

MLYCD p.Leu8fs (c.22_34del) is very rare (popmax 0.000426%, nfe) (gnomAD).

How is Malonic aciduria inherited?

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

MLYCD p.Leu8fs

c.22_34del · rs938617354 · VCV2890013

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.000426%, nfe)

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	28.3	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 0.000426% European (non-Finnish) · 4/937,894 alleles

Filtering AF 0.0001% ClinGen BA1/BS1 input FAF95, joint · FAF99 6.7e-05%

Overall 0.000435% 5/1,148,884 alleles · very rare exomes 4/999,224 · genomes 1/149,660 · joint denominator

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.00257%	38,918
European (non-Finnish)grpmax	0.000426%	234,474

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Leu8fs
Coding: c.22_34del
MANE Select: NM_012213
dbSNP: rs938617354
Type: Deletion
Location: chr16:83899158 (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-leu8fs (accessed [today's date]).

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