Is MLYCD p.Tyr75Phe (c.224A>T) pathogenic?

MLYCD p.Tyr75Phe (c.224A>T) is classified Uncertain significance in MLYCD (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-05-16). AlphaMissense: likely benign (0.3284); Very rare (popmax 0.00143%, afr); Associated with Inborn genetic diseases.

What condition is associated with MLYCD p.Tyr75Phe (c.224A>T)?

MLYCD p.Tyr75Phe (c.224A>T) is associated with Inborn genetic diseases (ClinVar).

How common is MLYCD p.Tyr75Phe (c.224A>T) in the general population?

MLYCD p.Tyr75Phe (c.224A>T) is very rare (popmax 0.00143%, afr) (gnomAD).

What do computational predictors say about MLYCD p.Tyr75Phe (c.224A>T)?

AlphaMissense predicts likely benign (score 0.3284) — an in-silico prediction, not a clinical call.

MLYCD p.Tyr75Phe

c.224A>T · rs745379940 · VCV1304741

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.3284 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00143%, afr)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.3284	likely benign
REVEL	0.807	moderately pathogenic-leaning
SaProt	LLR -10.84	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 10	GERP 1.3, phastCons 1
Regional constraint	o/e 1.38	unconstrained · MANE · 16 kb · p 1.5e-22 · regional, not allelic
Overall
CADD	25.4	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 0.00143% African / African-American · 1/70,076 alleles

Filtering AF 2.9e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000196% 3/1,527,358 alleles · very rare exomes 3/1,375,424 · genomes 0/151,934 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00143%	70,076
European (non-Finnish)	0.000174%	573,102

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.Tyr75Phe
Coding: c.224A>T
MANE Select: NM_012213
dbSNP: rs745379940
Type: single nucleotide variant
Location: chr16:83899368 (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 75: the 'alpha-helical 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.Tyr75Ter Pathogenic ★ same residue
MLYCD p.Tyr75= 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-tyr75phe (accessed [today's date]).

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