Is MLYCD p.Val181Met (c.541G>A) pathogenic?

MLYCD p.Val181Met (c.541G>A) is classified Benign/Likely benign in MLYCD (ClinVar, Multiple submitters, 3 submitters; last evaluated 2026-01-15). AlphaMissense: likely benign (0.211); Rare (popmax 0.929%, eas); Associated with malonic aciduria.

What condition is associated with MLYCD p.Val181Met (c.541G>A)?

MLYCD p.Val181Met (c.541G>A) is associated with malonic aciduria (ClinVar).

How common is MLYCD p.Val181Met (c.541G>A) in the general population?

MLYCD p.Val181Met (c.541G>A) is rare (popmax 0.929%, eas) (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.Val181Met (c.541G>A)?

AlphaMissense predicts likely benign (score 0.211) — an in-silico prediction, not a clinical call.

MLYCD p.Val181Met

c.541G>A · rs147617160 · VCV460445

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.211 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.929%, eas)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

malonic aciduria

Computational evidence

Protein change
AlphaMissense	0.211	likely benign
REVEL	0.477	indeterminate
SaProt	LLR -8.70	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 9.9	GERP 1.5, phastCons 1
Regional constraint	o/e 1.38	unconstrained · MANE · 16 kb · p 1.5e-22 · regional, not allelic
Overall
CADD	26.3	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.929% East Asian · 417/44,874 alleles

Filtering AF 0.856% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.827%

Overall 0.034% 548/1,614,024 alleles · rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.929%	108
Remaining individualsnot grpmax-eligible	0.126%	791
African / African-American	0.036%	2,779
South Asian	0.00878%	11,384
Admixed American	0.005%	20,007
European (non-Finnish)	0.00119%	84,279

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.Val181Met
Coding: c.541G>A
MANE Select: NM_012213
dbSNP: rs147617160
Type: single nucleotide variant
Location: chr16:83906999 (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 181: the 'alpha-helical domain' region; an α-helix

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.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
MLYCD p.Arg392Gln Uncertain significance ★★ ⚠ same condition
MLYCD p.Arg392Trp 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-val181met (accessed [today's date]).

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