Is MIPEP p.Asp247Ala (c.740A>C) pathogenic?

MIPEP p.Asp247Ala (c.740A>C) is classified Uncertain significance in MIPEP (ClinVar, Single submitter, 1 submitter; last evaluated 2025-09-26). AlphaMissense: likely benign (0.0976); Very rare (popmax 0.000254%, nfe); Associated with Inborn genetic diseases.

What condition is associated with MIPEP p.Asp247Ala (c.740A>C)?

MIPEP p.Asp247Ala (c.740A>C) is associated with Inborn genetic diseases (ClinVar).

How common is MIPEP p.Asp247Ala (c.740A>C) in the general population?

MIPEP p.Asp247Ala (c.740A>C) is very rare (popmax 0.000254%, nfe) (gnomAD).

What do computational predictors say about MIPEP p.Asp247Ala (c.740A>C)?

AlphaMissense predicts likely benign (score 0.0976) — an in-silico prediction, not a clinical call.

MIPEP p.Asp247Ala

c.740A>C · VCV4625018

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0976 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000254%, nfe)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0976	likely benign
REVEL	0.065	moderately benign-leaning
SaProt	LLR -10.97	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.64	GERP 1.6
Regional constraint	o/e 1.04	unconstrained · MANE · 159 kb · p 0.25 · regional, not allelic
Overall
CADD	14.24	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 0.000254% European (non-Finnish) · 3/1,179,154 alleles

Filtering AF 6.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.9e-05%

Overall 0.000186% 3/1,612,346 alleles · very rare exomes 3/1,460,126 · genomes 0/152,220 · joint denominator

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.Asp247Ala
Coding: c.740A>C
MANE Select: NM_005932
Type: single nucleotide variant
Location: chr13:23870059 (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-asp247ala (accessed [today's date]).

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