Is IPO8 p.Ser984= (c.2952C>T) pathogenic?

IPO8 p.Ser984= (c.2952C>T) is classified Likely benign in IPO8 (ClinVar, Single submitter, 2 submitters; last evaluated 2023-03-01). Very rare (popmax 0.00636%, nfe).

How common is IPO8 p.Ser984= (c.2952C>T) in the general population?

IPO8 p.Ser984= (c.2952C>T) is very rare (popmax 0.00636%, nfe) (gnomAD).

IPO8 p.Ser984=

c.2952C>T · rs746079753 · VCV2498551

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00636%, nfe)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.104	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.076	phastCons 0.071
Overall
CADD	7.38	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00636% European (non-Finnish) · 75/1,179,918 alleles

Filtering AF 0.00519% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00474%

Overall 0.00502% 81/1,612,798 alleles · very rare exomes 74/1,460,672 · genomes 7/152,126 · joint denominator

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.00641%	15,611
European (non-Finnish)grpmax	0.00636%	15,732
Admixed American	0.00167%	59,984
South Asian	0.0011%	91,050

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Ser984=
Coding: c.2952C>T
MANE Select: NM_006390
dbSNP: rs746079753
Type: single nucleotide variant
Location: chr12:30631959 (GRCh38)
Gene constraint: LOEUF 0.575 · pLI 0.15 (gnomAD)
Structure: AlphaFold pLDDT 87.59
Residue 984: 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); a UniProt-annotated variant site (in viss); a UniProt-annotated variant site (in viss; undetectable protein levels in patient's fibroblasts, although mrna levels seem unaffected)

Full IPO8 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

IPO8 c.2900-1G>A Pathogenic/Likely pathogenic ★★ same type
IPO8 p.Arg474Ter Pathogenic ★★ same type
IPO8 p.Arg803Ter Pathogenic/Likely pathogenic ★★ same type
IPO8 p.Trp259Ter Pathogenic ★★ same type
IPO8 p.Ala877Asp Uncertain significance ★★ ⚠ same type
IPO8 p.Ala941Val Uncertain significance ★★ ⚠ same type
IPO8 p.Arg1002Trp Uncertain significance ★★ ⚠ same type
IPO8 p.Arg884Gln 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/ipo8-p-ser984 (accessed [today's date]).

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