Is MIPEP p.Arg62Pro (c.185G>C) pathogenic?

MIPEP p.Arg62Pro (c.185G>C) is classified Uncertain significance in MIPEP (ClinVar, Single submitter, 1 submitter; last evaluated 2024-01-29). AlphaMissense: likely benign (0.1119); Rare (popmax 0.169%, afr); Associated with Inborn genetic diseases.

What condition is associated with MIPEP p.Arg62Pro (c.185G>C)?

MIPEP p.Arg62Pro (c.185G>C) is associated with Inborn genetic diseases (ClinVar).

How common is MIPEP p.Arg62Pro (c.185G>C) in the general population?

MIPEP p.Arg62Pro (c.185G>C) is rare (popmax 0.169%, afr) (gnomAD).

What do computational predictors say about MIPEP p.Arg62Pro (c.185G>C)?

AlphaMissense predicts likely benign (score 0.1119) — an in-silico prediction, not a clinical call.

MIPEP p.Arg62Pro

c.185G>C · rs554350439 · VCV3126688

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1119 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.169%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1119	likely benign
REVEL	0.1	moderately benign-leaning
SaProt	LLR -5.13	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 1.2	GERP -0.3, phastCons 1
Regional constraint	o/e 1.04	unconstrained · MANE · 159 kb · p 0.25 · regional, not allelic
Overall
CADD	22.9	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 0.169% African / African-American · 112/66,256 alleles

Filtering AF 0.144% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.134%

Overall 0.0085% 121/1,422,728 alleles · rare exomes 57/1,270,386 · genomes 64/152,342 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.169%	592
Remaining individualsnot grpmax-eligible	0.0112%	8,947
Admixed American	0.00965%	10,359

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: MIPEP
Protein: p.Arg62Pro
Coding: c.185G>C
MANE Select: NM_005932
dbSNP: rs554350439
Type: single nucleotide variant
Location: chr13:23889136 (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-arg62pro (accessed [today's date]).

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