Is MLYCD p.Ser447Cys (c.1340C>G) pathogenic?

MLYCD p.Ser447Cys (c.1340C>G) is classified Uncertain significance in MLYCD (ClinVar, Single submitter, 1 submitter; last evaluated 2024-08-04). AlphaMissense: likely benign (0.2613); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with MLYCD p.Ser447Cys (c.1340C>G)?

MLYCD p.Ser447Cys (c.1340C>G) is associated with Inborn genetic diseases (ClinVar).

How common is MLYCD p.Ser447Cys (c.1340C>G) in the general population?

MLYCD p.Ser447Cys (c.1340C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about MLYCD p.Ser447Cys (c.1340C>G)?

AlphaMissense predicts likely benign (score 0.2613) — an in-silico prediction, not a clinical call.

MLYCD p.Ser447Cys

c.1340C>G · VCV3396894

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2613 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.2613	likely benign
REVEL	0.89	moderately pathogenic-leaning
SaProt	LLR -12.52	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 7.5	GERP 1.4, phastCons 1
Regional constraint	o/e 1.38	unconstrained · MANE · 16 kb · p 1.5e-22 · regional, not allelic
Overall
CADD	26.6	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: MLYCD
Protein: p.Ser447Cys
Coding: c.1340C>G
MANE Select: NM_012213
Type: single nucleotide variant
Location: chr16:83915347 (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 447: the 'catalytic domain' region; an α-helix

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

Similar variants

MLYCD p.Ser447= Likely benign ★ same residue
MLYCD p.Ala119Ser Uncertain significance ★★ ⚠ same condition
MLYCD p.Arg199Gln Uncertain significance ★★ ⚠ same condition
MLYCD p.Arg235Gly Uncertain significance ★★ ⚠ same condition
MLYCD p.Arg392Trp Uncertain significance ★★ ⚠ same condition
MLYCD p.Arg432Cys Uncertain significance ★★ ⚠ same condition
MLYCD p.Arg455Cys Uncertain significance ★★ ⚠ same condition
MLYCD p.Gly108Val 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-ser447cys (accessed [today's date]).

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