Is MCEE p.Pro157Ser (c.469C>T) pathogenic?

MCEE p.Pro157Ser (c.469C>T) is classified Uncertain significance in MCEE (ClinVar, Single submitter, 1 submitter; last evaluated 2023-10-27). AlphaMissense: likely benign (0.3003); Ultra-rare (popmax 0.0233%, amr); Associated with Inborn genetic diseases.

What condition is associated with MCEE p.Pro157Ser (c.469C>T)?

MCEE p.Pro157Ser (c.469C>T) is associated with Inborn genetic diseases (ClinVar).

How common is MCEE p.Pro157Ser (c.469C>T) in the general population?

MCEE p.Pro157Ser (c.469C>T) is ultra-rare (popmax 0.0233%, amr) (gnomAD).

What do computational predictors say about MCEE p.Pro157Ser (c.469C>T)?

AlphaMissense predicts likely benign (score 0.3003) — an in-silico prediction, not a clinical call.

MCEE p.Pro157Ser

c.469C>T · rs374637897 · VCV3124211

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.3003 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0233%, amr)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.3003	likely benign
REVEL	0.508	indeterminate
SaProt	LLR -11.74	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 1.9, phastCons 1
Regional constraint	o/e 1.01	unconstrained · MANE · 20 kb · p 0.9 · regional, not allelic
Overall
CADD	26.9	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 0.0233% Admixed American · 14/59,968 alleles

Filtering AF 0.0141% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0112%

Overall 0.00223% 36/1,613,498 alleles · ultra-rare exomes 25/1,461,470 · genomes 11/152,028 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0233%	4,283
African / African-American	0.00801%	12,481
Remaining individualsnot grpmax-eligible	0.0064%	15,616
European (non-Finnish)	0.00102%	98,310

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.Pro157Ser
Coding: c.469C>T
MANE Select: NM_032601
dbSNP: rs374637897
Type: single nucleotide variant
Location: chr2:71110032 (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 157: the voc domain; a β-strand

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-pro157ser (accessed [today's date]).

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