Is INTS8 p.Glu794Val (c.2381A>T) pathogenic?

INTS8 p.Glu794Val (c.2381A>T) is classified Uncertain significance in INTS8 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-12-06). AlphaMissense: likely pathogenic (0.747); Very rare (popmax 0.00136%, nfe).

How common is INTS8 p.Glu794Val (c.2381A>T) in the general population?

INTS8 p.Glu794Val (c.2381A>T) is very rare (popmax 0.00136%, nfe) (gnomAD).

What do computational predictors say about INTS8 p.Glu794Val (c.2381A>T)?

AlphaMissense predicts likely pathogenic (score 0.747) — an in-silico prediction, not a clinical call.

INTS8 p.Glu794Val

c.2381A>T · rs1355858828 · VCV2264973

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.747 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00136%, nfe)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.747	likely pathogenic
REVEL	0.707	pathogenic-leaning
SaProt	LLR -7.01	tolerated
⇒ AlphaMissense and REVEL call this damaging; SaProt does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 1.4, phastCons 1
Regional constraint	o/e 0.85	unconstrained · MANE · 57 kb · p 2.4e-07 · regional, not allelic
Overall
CADD	29.5	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 0.00136% European (non-Finnish) · 16/1,179,062 alleles

Filtering AF 0.000803% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00065%

Overall 0.000992% 16/1,612,190 alleles · very rare exomes 15/1,460,138 · genomes 1/152,052 · joint denominator

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.Glu794Val
Coding: c.2381A>T
MANE Select: NM_017864
dbSNP: rs1355858828
Type: single nucleotide variant
Location: chr8:94867304 (GRCh38)
Gene constraint: LOEUF 0.453 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 84.47 · 10 PDB

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

Similar variants

INTS8 p.Tyr499Cys Uncertain significance ★★ ⚠ same type
INTS8 c.1018-11G>A Benign ★★ same type
INTS8 p.Ala898= Benign ★★ same type
INTS8 p.Gly437Glu Likely benign ★★ same type
INTS8 p.His922= Benign ★★ same type
INTS8 p.Ser710= Benign ★★ same type
INTS8 p.Ser755Arg Benign/Likely benign ★★ ⚠ same type
INTS8 p.Arg359Ter Likely pathogenic ★ 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-glu794val (accessed [today's date]).

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