Is MLYCD p.Pro205Ser (c.613C>T) pathogenic?

MLYCD p.Pro205Ser (c.613C>T) is classified Uncertain significance in MLYCD (ClinVar, Multiple submitters, 3 submitters; last evaluated 2022-06-27). AlphaMissense: likely benign (0.1105); Very rare (popmax 0.0061%, nfe); Associated with malonic aciduria.

What condition is associated with MLYCD p.Pro205Ser (c.613C>T)?

MLYCD p.Pro205Ser (c.613C>T) is associated with malonic aciduria (ClinVar).

How common is MLYCD p.Pro205Ser (c.613C>T) in the general population?

MLYCD p.Pro205Ser (c.613C>T) is very rare (popmax 0.0061%, nfe) (gnomAD).

How is Malonic aciduria inherited?

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

What do computational predictors say about MLYCD p.Pro205Ser (c.613C>T)?

AlphaMissense predicts likely benign (score 0.1105) — an in-silico prediction, not a clinical call.

MLYCD p.Pro205Ser

c.613C>T · rs759089126 · VCV320727

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.1105 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0061%, nfe)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

malonic aciduria

Computational evidence

Protein change
AlphaMissense	0.1105	likely benign
REVEL	0.469	indeterminate
SaProt	LLR -7.74	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.2	GERP -0.73, phastCons 0.98
Regional constraint	o/e 1.38	unconstrained · MANE · 16 kb · p 1.5e-22 · regional, not allelic
Overall
CADD	11.49	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0061% European (non-Finnish) · 72/1,179,948 alleles

Filtering AF 0.00495% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00455%

Overall 0.00459% 74/1,613,942 alleles · very rare exomes 73/1,461,784 · genomes 1/152,158 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0061%	16,388
Remaining individualsnot grpmax-eligible	0.0032%	31,243

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.Pro205Ser
Coding: c.613C>T
MANE Select: NM_012213
dbSNP: rs759089126
Type: single nucleotide variant
Location: chr16:83907071 (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 205: 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.Pro205= Likely benign ★ same residue
MLYCD p.Pro205Leu Uncertain significance ★ ⚠ same residue
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

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-pro205ser (accessed [today's date]).

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