Is IPO4 p.Asp1033Glu (c.3099C>A) pathogenic?

IPO4 p.Asp1033Glu (c.3099C>A) is classified Likely benign in IPO4 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-09-25). AlphaMissense: likely benign (0.0894); Ultra-rare (popmax 0.0799%, afr).

How common is IPO4 p.Asp1033Glu (c.3099C>A) in the general population?

IPO4 p.Asp1033Glu (c.3099C>A) is ultra-rare (popmax 0.0799%, afr) (gnomAD).

What do computational predictors say about IPO4 p.Asp1033Glu (c.3099C>A)?

AlphaMissense predicts likely benign (score 0.0894) — an in-silico prediction, not a clinical call.

IPO4 p.Asp1033Glu

c.3099C>A · VCV4679242

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0894 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0799%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0894	likely benign
REVEL	0.028	moderately benign-leaning
SaProt	LLR -4.38	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	GERP -5.4
Regional constraint	o/e 0.88	unconstrained · MANE · 3,885 bp · p 0.0022 · regional, not allelic
Overall
CADD	5.43	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 0.0799% African / African-American · 60/75,050 alleles

Filtering AF 0.0637% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0579%

Overall 0.00427% 69/1,614,156 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0799%	1,251
Admixed American	0.00833%	12,004
Remaining individualsnot grpmax-eligible	0.0064%	15,627

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: IPO4
Protein: p.Asp1033Glu
Coding: c.3099C>A
MANE Select: NM_024658
Type: single nucleotide variant
Location: chr14:24180705 (GRCh38)
Gene constraint: LOEUF 0.803 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 90.05 · 4 PDB

Full IPO4 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

IPO4 p.Arg20Cys Benign ★★ ⚠ same type
IPO4 p.Pro494Thr Benign ★★ same type
IMP4 p.Ala21Val Uncertain significance ★ ⚠ same type
IMP4 p.Ala282Thr Uncertain significance ★ ⚠ same type
IMP4 p.Arg126Gln Uncertain significance ★ ⚠ same type
IMP4 p.Arg170Trp Uncertain significance ★ ⚠ same type
IMP4 p.Arg194Cys Uncertain significance ★ ⚠ same type
IMP4 p.Arg198Gln Uncertain significance ★ ⚠ same type

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/ipo4-p-asp1033glu (accessed [today's date]).

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