Is IPO4 p.Arg11Trp (c.31C>T) pathogenic?

IPO4 p.Arg11Trp (c.31C>T) is classified Uncertain significance in IPO4 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-10-13). AlphaMissense: likely benign (0.176); Ultra-rare (popmax 0.0141%, nfe).

How common is IPO4 p.Arg11Trp (c.31C>T) in the general population?

IPO4 p.Arg11Trp (c.31C>T) is ultra-rare (popmax 0.0141%, nfe) (gnomAD).

What do computational predictors say about IPO4 p.Arg11Trp (c.31C>T)?

AlphaMissense predicts likely benign (score 0.176) — an in-silico prediction, not a clinical call.

IPO4 p.Arg11Trp

c.31C>T · rs542303871 · VCV2411572

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.176 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0141%, nfe)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.176	likely benign
REVEL	0.104	moderately benign-leaning
SaProt	LLR -12.40	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 2.2	GERP 0.59, phastCons 0.95
Regional constraint	o/e 0.99	unconstrained · MANE · 4,391 bp · p 0.73 · regional, not allelic
Overall
CADD	19.6	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 0.0141% European (non-Finnish) · 161/1,141,228 alleles

Filtering AF 0.0123% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0116%

Overall 0.0115% 176/1,533,918 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0141%	7,088
Admixed American	0.0123%	8,136
African / African-American	0.00689%	14,514
Remaining individualsnot grpmax-eligible	0.00511%	19,582
South Asian	0.00127%	78,892

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.Arg11Trp
Coding: c.31C>T
MANE Select: NM_024658
dbSNP: rs542303871
Type: single nucleotide variant
Location: chr14:24188757 (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-arg11trp (accessed [today's date]).

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