Is IPO8 p.Arg108= (c.324A>G) pathogenic?

IPO8 p.Arg108= (c.324A>G) is classified Likely benign in IPO8 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-08-19). Ultra-rare (popmax 0.0661%, mid); Associated with Inborn genetic diseases.

What condition is associated with IPO8 p.Arg108= (c.324A>G)?

IPO8 p.Arg108= (c.324A>G) is associated with Inborn genetic diseases (ClinVar).

How common is IPO8 p.Arg108= (c.324A>G) in the general population?

IPO8 p.Arg108= (c.324A>G) is ultra-rare (popmax 0.0661%, mid) (gnomAD).

IPO8 p.Arg108=

c.324A>G · rs774305257 · VCV3025391

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0661%, mid)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.3	GERP -1.3, phastCons 1
Overall
CADD	14.49	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0661% Middle Eastern · 4/6,050 alleles

Filtering AF 0.0268% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0228%

Overall 0.00293% 47/1,606,622 alleles · ultra-rare exomes 39/1,454,402 · genomes 8/152,220 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0661%	1,513
Admixed American	0.0393%	2,543
Ashkenazi Jewishnot grpmax-eligible	0.0103%	9,751
Remaining individualsnot grpmax-eligible	0.00482%	20,726
African / African-American	0.00134%	74,642
European (non-Finnish)	0.0011%	90,506

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: IPO8
Protein: p.Arg108=
Coding: c.324A>G
MANE Select: NM_006390
dbSNP: rs774305257
Type: single nucleotide variant
Location: chr12:30681817 (GRCh38)
Gene constraint: LOEUF 0.575 · pLI 0.15 (gnomAD)
Structure: AlphaFold pLDDT 87.59
Residue 108: a UniProt-annotated variant site (in viss; undetectable protein levels in either patient's fibroblasts or patient's epstein-barr virus-immortalized b cell lines)

Full IPO8 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

IPO8 p.Ala877Asp Uncertain significance ★★ ⚠ same condition
IPO8 p.Ala941Val Uncertain significance ★★ ⚠ same condition
IPO8 p.Arg1002Trp Uncertain significance ★★ ⚠ same condition
IPO8 p.Arg884Gln Uncertain significance ★★ ⚠ same condition
IPO8 p.Asn953Asp Uncertain significance ★★ ⚠ same condition
IPO8 p.His435Arg Uncertain significance ★★ ⚠ same condition
IPO8 p.Lys533Asn Uncertain significance ★★ ⚠ same condition
IPO8 p.Pro423Leu 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/ipo8-p-arg108 (accessed [today's date]).

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