Is INTS8 p.Glu100= (c.300G>A) pathogenic?

INTS8 p.Glu100= (c.300G>A) is classified Likely benign in INTS8 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-12-23). Rare (popmax 0.314%, afr); Associated with INTS8-related disorder.

What condition is associated with INTS8 p.Glu100= (c.300G>A)?

INTS8 p.Glu100= (c.300G>A) is associated with INTS8-related disorder (ClinVar).

How common is INTS8 p.Glu100= (c.300G>A) in the general population?

INTS8 p.Glu100= (c.300G>A) is rare (popmax 0.314%, afr) (gnomAD).

INTS8 p.Glu100=

c.300G>A · rs141032302 · VCV3040489

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

rare (popmax 0.314%, afr)

Conditions

INTS8-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.409	indeterminate
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 2.6	GERP -1, phastCons 1
Overall
CADD	9.231	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.314% African / African-American · 233/74,232 alleles

Filtering AF 0.281% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.268%

Overall 0.0197% 314/1,594,878 alleles · rare exomes 182/1,442,676 · genomes 132/152,202 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.314%	319
Remaining individualsnot grpmax-eligible	0.0292%	3,430
Admixed American	0.0208%	4,814
Middle Eastern	0.0169%	5,930
European (non-Finnish)	0.00429%	23,336

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: INTS8
Protein: p.Glu100=
Coding: c.300G>A
MANE Select: NM_017864
dbSNP: rs141032302
Type: single nucleotide variant
Location: chr8:94825062 (GRCh38)
Gene constraint: LOEUF 0.453 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 84.47 · 10 PDB
Residue 100: an α-helix

Full INTS8 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

INTS8-related disorder

Similar variants

INTS8 c.2762+1G>A Uncertain significance ★ same condition
INTS8 c.131-9A>G Benign same condition
INTS8 c.2077-8T>C Benign same condition
INTS8 p.Ile816Val Likely benign same condition
INTS8 p.Ile828Val Likely benign same condition
INTS8 p.Thr677= Likely benign same condition
INTS8 p.Tyr499Cys Uncertain significance ★★ ⚠ same type
INTS8 c.1018-11G>A Benign ★★ 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/ints8-p-glu100 (accessed [today's date]).

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