Is MIPEP p.Ser288Arg (c.862A>C) pathogenic?

MIPEP p.Ser288Arg (c.862A>C) is classified Benign/Likely benign in MIPEP (ClinVar, Multiple submitters, 4 submitters; last evaluated 2026-01-08). AlphaMissense: likely benign (0.2973); Rare (popmax 0.113%, sas); Associated with Inborn genetic diseases.

What condition is associated with MIPEP p.Ser288Arg (c.862A>C)?

MIPEP p.Ser288Arg (c.862A>C) is associated with Inborn genetic diseases (ClinVar).

How common is MIPEP p.Ser288Arg (c.862A>C) in the general population?

MIPEP p.Ser288Arg (c.862A>C) is rare (popmax 0.113%, sas) (gnomAD).

What do computational predictors say about MIPEP p.Ser288Arg (c.862A>C)?

AlphaMissense predicts likely benign (score 0.2973) — an in-silico prediction, not a clinical call.

MIPEP p.Ser288Arg

c.862A>C · rs149856612 · VCV1584733

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

AlphaMissense

likely benign

0.2973 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.113%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.2973	likely benign
REVEL	0.114	moderately benign-leaning
SaProt	LLR -9.87	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 1.5	GERP 1.4, phastCons 0.009
Regional constraint	o/e 1.04	unconstrained · MANE · 159 kb · p 0.25 · regional, not allelic
Overall
CADD	21.9	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 0.113% South Asian · 103/90,962 alleles

Filtering AF 0.0954% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0889%

Overall 0.0847% 1,367/1,613,742 alleles · rare

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	0.653%	153
South Asiangrpmax	0.113%	883
Remaining individualsnot grpmax-eligible	0.072%	1,389
European (non-Finnish)	0.0672%	1,488
Admixed American	0.01%	9,972
African / African-American	0.00266%	37,529

Finnish 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.Ser288Arg
Coding: c.862A>C
MANE Select: NM_005932
dbSNP: rs149856612
Type: single nucleotide variant
Location: chr13:23869373 (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-ser288arg (accessed [today's date]).

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