Is INTS8 p.Ile828Val (c.2482A>G) pathogenic?

INTS8 p.Ile828Val (c.2482A>G) is classified Likely benign in INTS8 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-11-25). AlphaMissense: likely benign (0.0706); Rare (popmax 0.456%, amr); Associated with INTS8-related disorder.

What condition is associated with INTS8 p.Ile828Val (c.2482A>G)?

INTS8 p.Ile828Val (c.2482A>G) is associated with INTS8-related disorder (ClinVar).

How common is INTS8 p.Ile828Val (c.2482A>G) in the general population?

INTS8 p.Ile828Val (c.2482A>G) is rare (popmax 0.456%, amr) (gnomAD).

What do computational predictors say about INTS8 p.Ile828Val (c.2482A>G)?

AlphaMissense predicts likely benign (score 0.0706) — an in-silico prediction, not a clinical call.

INTS8 p.Ile828Val

c.2482A>G · rs140060323 · VCV3034286

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0706 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.456%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

INTS8-related disorder

Computational evidence

Protein change
AlphaMissense	0.0706	likely benign
REVEL	0.075	moderately benign-leaning
SaProt	LLR -5.43	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.7	GERP 1.9, phastCons 1
Regional constraint	o/e 0.85	unconstrained · MANE · 57 kb · p 2.4e-07 · regional, not allelic
Overall
CADD	11.99	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

Grpmax group 0.456% Admixed American · 272/59,586 alleles

Filtering AF 0.412% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.395%

Overall 0.0177% 285/1,606,076 alleles · rare exomes 247/1,453,836 · genomes 38/152,240 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.456%	219
African / African-American	0.00669%	14,954
Remaining individualsnot grpmax-eligible	0.00322%	31,102
European (non-Finnish)	0.000511%	195,611

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.Ile828Val
Coding: c.2482A>G
MANE Select: NM_017864
dbSNP: rs140060323
Type: single nucleotide variant
Location: chr8:94871951 (GRCh38)
Gene constraint: LOEUF 0.453 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 84.47 · 10 PDB
Residue 828: 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.Glu100= Likely benign same condition
INTS8 p.Ile816Val 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-ile828val (accessed [today's date]).

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