Is IPO4 p.Asp656Asn (c.1966G>A) pathogenic?

IPO4 p.Asp656Asn (c.1966G>A) is classified Uncertain significance in IPO4 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-06-30). AlphaMissense: likely benign (0.0897); Absent from gnomAD v4.1.

How common is IPO4 p.Asp656Asn (c.1966G>A) in the general population?

IPO4 p.Asp656Asn (c.1966G>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about IPO4 p.Asp656Asn (c.1966G>A)?

AlphaMissense predicts likely benign (score 0.0897) — an in-silico prediction, not a clinical call.

IPO4 p.Asp656Asn

c.1966G>A · rs2502147571 · VCV2607166

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0897 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0897	likely benign
REVEL	0.154	moderately benign-leaning
SaProt	LLR -8.11	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>A here scores Δ0.82 · evaluated, not missing
Constraint at this position
Conservation	phyloP 2.6	GERP 1.6, phastCons 0.98
Regional constraint	o/e 0.88	unconstrained · MANE · 3,885 bp · p 0.0022 · regional, not allelic
Overall
CADD	18.83	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: IPO4
Protein: p.Asp656Asn
Coding: c.1966G>A
MANE Select: NM_024658
dbSNP: rs2502147571
Type: single nucleotide variant
Location: chr14:24183802 (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-asp656asn (accessed [today's date]).

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