Is MCEE p.Phe64Leu (c.192T>G) pathogenic?

MCEE p.Phe64Leu (c.192T>G) is classified Uncertain significance in MCEE (ClinVar, Single submitter, 1 submitter; last evaluated 2024-10-09). AlphaMissense: likely pathogenic (0.8923); Ultra-rare (popmax 0.0117%, amr); Associated with Inborn genetic diseases.

What condition is associated with MCEE p.Phe64Leu (c.192T>G)?

MCEE p.Phe64Leu (c.192T>G) is associated with Inborn genetic diseases (ClinVar).

How common is MCEE p.Phe64Leu (c.192T>G) in the general population?

MCEE p.Phe64Leu (c.192T>G) is ultra-rare (popmax 0.0117%, amr) (gnomAD).

What do computational predictors say about MCEE p.Phe64Leu (c.192T>G)?

AlphaMissense predicts likely pathogenic (score 0.8923) — an in-silico prediction, not a clinical call.

MCEE p.Phe64Leu

c.192T>G · VCV3544088

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8923 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0117%, amr)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.8923	likely pathogenic
REVEL	0.18	moderately benign-leaning
SaProt	LLR -9.58	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.6	GERP 0.6, phastCons 1
Regional constraint	o/e 1.01	unconstrained · MANE · 20 kb · p 0.9 · regional, not allelic
Overall
CADD	15.24	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 0.0117% Admixed American · 7/59,986 alleles

Filtering AF 0.00543% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00381%

Overall 0.00198% 32/1,614,024 alleles · ultra-rare exomes 27/1,461,886 · genomes 5/152,138 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0117%	8,569
Remaining individualsnot grpmax-eligible	0.008%	12,496
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,608
European (non-Finnish)	0.00161%	62,108

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: MCEE
Protein: p.Phe64Leu
Coding: c.192T>G
MANE Select: NM_032601
Type: single nucleotide variant
Location: chr2:71124392 (GRCh38)
Gene constraint: LOEUF 0.867 · pLI 0.41 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 87.27 · 2 PDB
Residue 64: an α-helix; the voc domain

Full MCEE 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

MCEE p.Asn115Lys Uncertain significance ★★ ⚠ same condition
MCEE p.Ile159Thr Uncertain significance ★★ ⚠ same condition
MCEE p.Leu79Val Uncertain significance ★★ ⚠ same condition
MCEE p.Ala10Thr Uncertain significance ★ ⚠ same condition
MCEE p.Ala2Val Uncertain significance ★ ⚠ same condition
MCEE p.Ala63Glu Uncertain significance ★ ⚠ same condition
MCEE p.Ala76Thr Uncertain significance ★ ⚠ same condition
MCEE p.Asn115Ser 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/mcee-p-phe64leu (accessed [today's date]).

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