Is INTS8 p.Asp298Gly (c.893A>G) pathogenic?

INTS8 p.Asp298Gly (c.893A>G) is classified Pathogenic in INTS8 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-09-11). AlphaMissense: likely pathogenic (0.5695); Absent from gnomAD v4.1; Associated with neurodevelopmental disorder with cerebellar hypoplasia and spasticity.

What condition is associated with INTS8 p.Asp298Gly (c.893A>G)?

INTS8 p.Asp298Gly (c.893A>G) is associated with neurodevelopmental disorder with cerebellar hypoplasia and spasticity (ClinVar).

How common is INTS8 p.Asp298Gly (c.893A>G) in the general population?

INTS8 p.Asp298Gly (c.893A>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about INTS8 p.Asp298Gly (c.893A>G)?

AlphaMissense predicts likely pathogenic (score 0.5695) — an in-silico prediction, not a clinical call.

INTS8 p.Asp298Gly

c.893A>G · rs1586479593 · VCV689526

Pathogenic No assertion criteria

Classification

Pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.5695 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

neurodevelopmental disorder with cerebellar hypoplasia and spasticity

Computational evidence

Protein change
AlphaMissense	0.5695	likely pathogenic ✓ concordant with ClinVar
REVEL	0.527	indeterminate
SaProt	LLR -12.39	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL is indeterminate.
Splicing
SpliceAI	Δ0.44	acceptor loss · deltas
Pangolin	Δ0.47	loss · gain 0.38 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 11	GERP 1.7, phastCons 1
Regional constraint	o/e 0.85	unconstrained · MANE · 57 kb · p 2.4e-07 · regional, not allelic
Overall
CADD	29.1	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

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: INTS8
Protein: p.Asp298Gly
Coding: c.893A>G
MANE Select: NM_017864
dbSNP: rs1586479593
Type: single nucleotide variant
Location: chr8:94838494 (GRCh38)
Gene constraint: LOEUF 0.453 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 84.47 · 10 PDB
Residue 298: a UniProt-annotated variant site (in nedchs; occurs in a splice site resulting in altered splicing and probable nonsense-mediated mrna decay)

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

Disease context

neurodevelopmental disorder with cerebellar hypoplasia and spasticity — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

INTS8 p.Tyr499Cys Uncertain significance ★★ ⚠ same condition
INTS8 c.1018-11G>A Benign ★★ same condition
INTS8 p.Ala898= Benign ★★ same condition
INTS8 p.Ser710= Benign ★★ same condition
INTS8 p.Arg359Ter Likely pathogenic ★ same condition
INTS8 p.Gln955Glu Uncertain significance ★ ⚠ same condition
INTS8 p.Glu973_Leu975del Pathogenic same condition
INTS8 p.Gly437Glu Likely 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-asp298gly (accessed [today's date]).

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