Is MLYCD p.Ala415Val (c.1244C>T) pathogenic?

MLYCD p.Ala415Val (c.1244C>T) is classified Uncertain significance in MLYCD (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-20). AlphaMissense: ambiguous (0.4136); Very rare (popmax 0.004%, afr); Associated with Inborn genetic diseases.

What condition is associated with MLYCD p.Ala415Val (c.1244C>T)?

MLYCD p.Ala415Val (c.1244C>T) is associated with Inborn genetic diseases (ClinVar).

How common is MLYCD p.Ala415Val (c.1244C>T) in the general population?

MLYCD p.Ala415Val (c.1244C>T) is very rare (popmax 0.004%, afr) (gnomAD).

What do computational predictors say about MLYCD p.Ala415Val (c.1244C>T)?

AlphaMissense predicts ambiguous (score 0.4136) — an in-silico prediction, not a clinical call.

MLYCD p.Ala415Val

c.1244C>T · VCV4108865

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4136 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.004%, afr)

Missense predictors

2/2 damaging

REVEL, SaProt · AlphaMissense no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.4136	ambiguous
REVEL	0.865	moderately pathogenic-leaning
SaProt	LLR -12.21	damaging
⇒ REVEL and SaProt both call this damaging; AlphaMissense makes no call.
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	27.2	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 0.004% African / African-American · 3/74,912 alleles

Filtering AF 0.00106% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000495%

Overall 0.00105% 17/1,612,498 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.004%	24,971
Remaining individualsnot grpmax-eligible	0.0016%	62,438
European (non-Finnish)	0.0011%	90,673

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.Ala415Val
Coding: c.1244C>T
MANE Select: NM_012213
Type: single nucleotide variant
Location: chr16:83915251 (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 415: the 'catalytic domain' region; a β-strand

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.Ala415Thr Uncertain significance ★★ ⚠ same residue
MLYCD p.Ala415= 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

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-ala415val (accessed [today's date]).

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