Is MLYCD p.Phe355fs (c.1064_1065del) pathogenic?

MLYCD p.Phe355fs (c.10641065del) is classified Pathogenic in MLYCD (ClinVar, No assertion criteria, 1 submitter; last evaluated 1999-08-27). Very rare (popmax 8.47e-05%, nfe); Associated with malonic aciduria.

What condition is associated with MLYCD p.Phe355fs (c.1064_1065del)?

MLYCD p.Phe355fs (c.1064_1065del) is associated with malonic aciduria (ClinVar).

How common is MLYCD p.Phe355fs (c.1064_1065del) in the general population?

MLYCD p.Phe355fs (c.1064_1065del) is very rare (popmax 8.47e-05%, nfe) (gnomAD).

How is Malonic aciduria inherited?

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

MLYCD p.Phe355fs

c.1064_1065del · rs1567636915 · VCV4058

Pathogenic No assertion criteria

Classification

Pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 8.47e-05%, nfe)

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	escapes	premature termination codon in the last exon (5 of 5) — the truncated protein is likely expressed. PVS1 input, not an applied code
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -0.43	GERP -2.8, phastCons 0.004

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.47e-05% European (non-Finnish) · 1/1,180,052 alleles

Overall 6.19e-05% 1/1,614,250 alleles · very rare exomes 1/1,461,894 · genomes 0/152,356 · joint denominator

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.Phe355fs
Coding: c.1064_1065del
MANE Select: NM_012213
dbSNP: rs1567636915
Type: Deletion
Location: chr16:83915070 (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 355: 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.Phe355_Thr356insPhePhePhePhePhePheXaaXaaXaaXaaArgAspProProAlaSerAlaSerGlnSerAlaGlyIleThrGlyValSerHisArgAlaArgProArgAsnGluLeuPhe Likely pathogenic ★ same residue
MLYCD p.Phe355= Likely benign ★ same residue
MLYCD p.Arg21fs Pathogenic/Likely pathogenic ★★ same condition
MLYCD p.Asn179fs Pathogenic ★ same condition
MLYCD p.Asp148fs Likely pathogenic ★ same condition
MLYCD p.Gln83fs Pathogenic ★ same condition
MLYCD p.Gly369fs Likely pathogenic ★ same condition
MLYCD p.Leu133fs 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-phe355fs (accessed [today's date]).

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