Is MLYCD p.Ser387Trp (c.1160C>G) pathogenic?

MLYCD p.Ser387Trp (c.1160C>G) is classified Uncertain significance in MLYCD (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-01-19). AlphaMissense: likely benign (0.2954); Ultra-rare (popmax 0.036%, afr); Associated with Inborn genetic diseases.

What condition is associated with MLYCD p.Ser387Trp (c.1160C>G)?

MLYCD p.Ser387Trp (c.1160C>G) is associated with Inborn genetic diseases, malonic aciduria (ClinVar).

How common is MLYCD p.Ser387Trp (c.1160C>G) in the general population?

MLYCD p.Ser387Trp (c.1160C>G) is ultra-rare (popmax 0.036%, afr) (gnomAD).

What do computational predictors say about MLYCD p.Ser387Trp (c.1160C>G)?

AlphaMissense predicts likely benign (score 0.2954) — an in-silico prediction, not a clinical call.

MLYCD p.Ser387Trp

c.1160C>G · rs376324546 · VCV450855

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.2954 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.036%, afr)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.2954	likely benign
REVEL	0.694	pathogenic-leaning
SaProt	LLR -12.10	damaging
⇒ REVEL and SaProt call this damaging; AlphaMissense does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.8	GERP 1.4, phastCons 1
Regional constraint	o/e 1.38	unconstrained · MANE · 16 kb · p 1.5e-22 · regional, not allelic
Overall
CADD	24.3	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 0.036% African / African-American · 27/74,946 alleles

Filtering AF 0.0254% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0219%

Overall 0.0018% 29/1,614,046 alleles · ultra-rare exomes 13/1,461,794 · genomes 16/152,252 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.036%	2,776
Remaining individualsnot grpmax-eligible	0.0032%	31,237

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.Ser387Trp
Coding: c.1160C>G
MANE Select: NM_012213
dbSNP: rs376324546
Type: single nucleotide variant
Location: chr16:83915167 (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 387: the 'catalytic domain' region

Full MLYCD gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: malonic aciduria

Similar variants

MLYCD p.Ser387Leu Uncertain significance ★★ ⚠ same residue
MLYCD p.Ser387= Likely benign ★ 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-ser387trp (accessed [today's date]).

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