Is IPO4 p.Asp575Asn (c.1723G>A) pathogenic?

IPO4 p.Asp575Asn (c.1723G>A) is classified Likely benign in IPO4 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-08-02). AlphaMissense: likely benign (0.0622); Rare (popmax 0.15%, mid).

How common is IPO4 p.Asp575Asn (c.1723G>A) in the general population?

IPO4 p.Asp575Asn (c.1723G>A) is rare (popmax 0.15%, mid) (gnomAD).

What do computational predictors say about IPO4 p.Asp575Asn (c.1723G>A)?

AlphaMissense predicts likely benign (score 0.0622) — an in-silico prediction, not a clinical call.

IPO4 p.Asp575Asn

c.1723G>A · rs780298284 · VCV2211450

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0622 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.15%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0622	likely benign
REVEL	0.106	moderately benign-leaning
SaProt	LLR -5.62	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 -0.81	GERP -2.9
Regional constraint	o/e 0.31	constrained · MANE · 64 bp · p 0.00024 · regional, not allelic
Overall
CADD	13.61	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 0.15% Middle Eastern · 9/5,988 alleles

Filtering AF 0.0783% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0585%

Overall 0.00459% 73/1,589,492 alleles · rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.15%	665
Remaining individualsnot grpmax-eligible	0.0114%	8,791
Ashkenazi Jewishnot grpmax-eligible	0.0103%	9,685
European (non-Finnish)	0.00462%	21,632

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.Asp575Asn
Coding: c.1723G>A
MANE Select: NM_024658
dbSNP: rs780298284
Type: single nucleotide variant
Location: chr14:24184332 (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.Asp575Glu Uncertain significance ★ ⚠ same residue
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

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-asp575asn (accessed [today's date]).

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