Is INTS8 p.Ser710= (c.2130T>C) pathogenic?

INTS8 p.Ser710= (c.2130T>C) is classified Benign in INTS8 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2021-08-19). Common (popmax 65.1%, eas) — too common for a highly-penetrant pathogenic allele; Associated with neurodevelopmental disorder with cerebellar hypoplasia and spasticity.

What condition is associated with INTS8 p.Ser710= (c.2130T>C)?

INTS8 p.Ser710= (c.2130T>C) is associated with neurodevelopmental disorder with cerebellar hypoplasia and spasticity (ClinVar).

INTS8 p.Ser710=

Q: How common is INTS8 p.Ser710= (c.2130T>C) in the general population?

INTS8 p.Ser710= (c.2130T>C) is common (popmax 65.1%, eas) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.2130T>C · rs713113 · VCV1300113

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Common

common (popmax 65.1%, eas) — too common for a highly-penetrant pathogenic allele

Conditions

neurodevelopmental disorder with cerebellar hypoplasia and spasticity

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.11	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.76	GERP 0.33, phastCons 0.018
Overall
CADD	8.409	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 65.1% East Asian · 29,186/44,856 alleles

Filtering AF 64.4% ClinGen BA1/BS1 input FAF95, joint · FAF99 64.2%

Overall 53.3% 859,427/1,613,356 alleles · common exomes 780,216/1,461,342 · genomes 79,211/152,014 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	65.1%	2
Amishnot grpmax-eligible	62.5%	2
South Asian	62.4%	2
Admixed American	61.8%	2
Ashkenazi Jewishnot grpmax-eligible	56.5%	2
Remaining individualsnot grpmax-eligible	54.9%	2
Middle Eastern	54.1%	2
Finnishnot grpmax-eligible	51.9%	2
European (non-Finnish)	51.8%	2
African / African-American	49.3%	2

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.Ser710=
Coding: c.2130T>C
MANE Select: NM_017864
dbSNP: rs713113
Type: single nucleotide variant
Location: chr8:94865559 (GRCh38)
Gene constraint: LOEUF 0.453 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 84.47 · 10 PDB
Residue 710: an α-helix

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.Arg359Ter Likely pathogenic ★ same condition
INTS8 p.Gln955Glu Uncertain significance ★ ⚠ same condition
INTS8 p.Asp298Gly Pathogenic 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-ser710 (accessed [today's date]).

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