Is MPI p.Arg5Leu (c.14G>T) pathogenic?

MPI p.Arg5Leu (c.14G>T) is classified Uncertain significance in MPI (ClinVar, Single submitter, 1 submitter; last evaluated 2024-01-16). AlphaMissense: likely benign (0.2447); Ultra-rare (popmax 0.0167%, mid); Associated with Inborn genetic diseases.

What condition is associated with MPI p.Arg5Leu (c.14G>T)?

MPI p.Arg5Leu (c.14G>T) is associated with Inborn genetic diseases (ClinVar).

How common is MPI p.Arg5Leu (c.14G>T) in the general population?

MPI p.Arg5Leu (c.14G>T) is ultra-rare (popmax 0.0167%, mid) (gnomAD).

What do computational predictors say about MPI p.Arg5Leu (c.14G>T)?

AlphaMissense predicts likely benign (score 0.2447) — an in-silico prediction, not a clinical call.

MPI p.Arg5Leu

c.14G>T · rs759385120 · VCV3202248

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2447 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0167%, mid)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.2447	likely benign
REVEL	0.585	indeterminate
SaProt	LLR -6.66	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.46	GERP -4.1, phastCons 0.017
Regional constraint	o/e 0.98	unconstrained · MANE · 7,653 bp · p 0.66 · regional, not allelic
Overall
CADD	19.05	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

Grpmax group 0.0167% Middle Eastern · 1/5,978 alleles

Filtering AF 0.000429% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000312%

Overall 0.000808% 13/1,608,070 alleles · ultra-rare exomes 10/1,455,834 · genomes 3/152,236 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0167%	5,978
Admixed American	0.00167%	60,002
African / African-American	0.00133%	74,940
European (non-Finnish)	0.000847%	117,998

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: MPI
Protein: p.Arg5Leu
Coding: c.14G>T
MANE Select: NM_002435
dbSNP: rs759385120
Type: single nucleotide variant
Location: chr15:74890087 (GRCh38)
Gene constraint: LOEUF 1.04 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 96.50

Full MPI 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

MPI p.Arg5Ter Pathogenic/Likely pathogenic ★★ same residue
MPI p.Arg5= Uncertain significance same residue
MPI p.Asn273Ser Uncertain significance ★★ ⚠ same condition
MPI p.Asp80Asn Uncertain significance ★★ ⚠ same condition
MPI p.Glu331Ala Uncertain significance ★★ ⚠ same condition
MPI p.Lys360Arg Uncertain significance ★★ ⚠ same condition
MPI p.Pro326Ser Uncertain significance ★★ ⚠ same condition
MPI p.Thr177Ile 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/mpi-p-arg5leu (accessed [today's date]).

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