Is MLYCD p.Pro63Ser (c.187C>T) pathogenic?

MLYCD p.Pro63Ser (c.187C>T) is classified Uncertain significance in MLYCD (ClinVar, Single submitter, 1 submitter; last evaluated 2023-06-26). AlphaMissense: likely benign (0.1454); Very rare (popmax 8.81e-05%, nfe); Associated with Inborn genetic diseases.

What condition is associated with MLYCD p.Pro63Ser (c.187C>T)?

MLYCD p.Pro63Ser (c.187C>T) is associated with Inborn genetic diseases (ClinVar).

How common is MLYCD p.Pro63Ser (c.187C>T) in the general population?

MLYCD p.Pro63Ser (c.187C>T) is very rare (popmax 8.81e-05%, nfe) (gnomAD).

What do computational predictors say about MLYCD p.Pro63Ser (c.187C>T)?

AlphaMissense predicts likely benign (score 0.1454) — an in-silico prediction, not a clinical call.

MLYCD p.Pro63Ser

c.187C>T · rs754001030 · VCV2606539

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1454 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.81e-05%, nfe)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1454	likely benign
REVEL	0.406	indeterminate
SaProt	LLR -0.29	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 3.6	GERP 1.3, phastCons 1
Regional constraint	o/e 1.38	unconstrained · MANE · 16 kb · p 1.5e-22 · regional, not allelic
Overall
CADD	20.5	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 8.81e-05% European (non-Finnish) · 1/1,134,600 alleles

Overall 7.39e-05% 1/1,353,716 alleles · very rare

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.Pro63Ser
Coding: c.187C>T
MANE Select: NM_012213
dbSNP: rs754001030
Type: single nucleotide variant
Location: chr16:83899331 (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 63: the 'alpha-helical 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

Similar variants

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
MLYCD p.Gly149Asp 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-pro63ser (accessed [today's date]).

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