Is MIPEP p.Pro18Leu (c.53C>T) pathogenic?

MIPEP p.Pro18Leu (c.53C>T) is classified Uncertain significance in MIPEP (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-29). AlphaMissense: likely benign (0.1114); No allele count reported in gnomAD v4.1 (AN 1,383,016); Associated with Inborn genetic diseases.

What condition is associated with MIPEP p.Pro18Leu (c.53C>T)?

MIPEP p.Pro18Leu (c.53C>T) is associated with Inborn genetic diseases (ClinVar).

How common is MIPEP p.Pro18Leu (c.53C>T) in the general population?

MIPEP p.Pro18Leu (c.53C>T) is no allele count reported in gnomAD v4.1 (AN 1,383,016) (gnomAD).

What do computational predictors say about MIPEP p.Pro18Leu (c.53C>T)?

AlphaMissense predicts likely benign (score 0.1114) — an in-silico prediction, not a clinical call.

MIPEP p.Pro18Leu

c.53C>T · VCV4108199

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1114 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,383,016)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1114	likely benign
REVEL	0.022	moderately benign-leaning
SaProt	LLR -3.09	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.25	GERP -3
Regional constraint	o/e 1.04	unconstrained · MANE · 159 kb · p 0.25 · regional, not allelic
Overall
CADD	2.564	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

No allele count reported in gnomAD v4.1 (AN 1,383,016). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: MIPEP
Protein: p.Pro18Leu
Coding: c.53C>T
MANE Select: NM_005932
Type: single nucleotide variant
Location: chr13:23889268 (GRCh38)
Gene constraint: LOEUF 1.181 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 90.33

Full MIPEP 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

MIPEP p.Ala138Val Uncertain significance ★★ ⚠ same condition
MIPEP p.Arg366Cys Uncertain significance ★★ same condition
MIPEP p.Arg453His Uncertain significance ★★ ⚠ same condition
MIPEP p.Arg509His Uncertain significance ★★ ⚠ same condition
MIPEP p.Arg560His Uncertain significance ★★ ⚠ same condition
MIPEP p.Arg621Gln Uncertain significance ★★ same condition
MIPEP p.Arg662Cys Uncertain significance ★★ ⚠ same condition
MIPEP p.Asp168Ala 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/mipep-p-pro18leu (accessed [today's date]).

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