Is MIPEP p.Pro688Ser (c.2062C>T) pathogenic?

MIPEP p.Pro688Ser (c.2062C>T) is classified Uncertain significance in MIPEP (ClinVar, Single submitter, 1 submitter; last evaluated 2025-10-29). AlphaMissense: likely pathogenic (0.5967); Very rare (popmax 0.00764%, nfe); Associated with Inborn genetic diseases.

What condition is associated with MIPEP p.Pro688Ser (c.2062C>T)?

MIPEP p.Pro688Ser (c.2062C>T) is associated with Inborn genetic diseases (ClinVar).

How common is MIPEP p.Pro688Ser (c.2062C>T) in the general population?

MIPEP p.Pro688Ser (c.2062C>T) is very rare (popmax 0.00764%, nfe) (gnomAD).

What do computational predictors say about MIPEP p.Pro688Ser (c.2062C>T)?

AlphaMissense predicts likely pathogenic (score 0.5967) — an in-silico prediction, not a clinical call.

MIPEP p.Pro688Ser

c.2062C>T · VCV4625017

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.5967 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00764%, nfe)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.5967	likely pathogenic
REVEL	0.233	benign-leaning
SaProt	LLR -12.75	damaging
⇒ AlphaMissense and SaProt call this damaging; REVEL does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 1.9, phastCons 1
Regional constraint	o/e 1.04	unconstrained · MANE · 159 kb · p 0.25 · regional, not allelic
Overall
CADD	28.2	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 0.00764% European (non-Finnish) · 90/1,177,668 alleles

Filtering AF 0.00632% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00585%

Overall 0.00596% 96/1,610,720 alleles · very rare exomes 89/1,458,530 · genomes 7/152,190 · joint denominator

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.00962%	10,390
European (non-Finnish)grpmax	0.00764%	13,085

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Pro688Ser
Coding: c.2062C>T
MANE Select: NM_005932
Type: single nucleotide variant
Location: chr13:23730428 (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-pro688ser (accessed [today's date]).

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