Is INTS8 p.Glu906Lys (c.2716G>A) pathogenic?

INTS8 p.Glu906Lys (c.2716G>A) is classified Uncertain significance in INTS8 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-01-16). AlphaMissense: likely pathogenic (0.755); Absent from gnomAD v4.1.

How common is INTS8 p.Glu906Lys (c.2716G>A) in the general population?

INTS8 p.Glu906Lys (c.2716G>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about INTS8 p.Glu906Lys (c.2716G>A)?

AlphaMissense predicts likely pathogenic (score 0.755) — an in-silico prediction, not a clinical call.

INTS8 p.Glu906Lys

c.2716G>A · rs2131078812 · VCV3110239

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.755 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.755	likely pathogenic
REVEL	0.425	indeterminate
SaProt	LLR -7.95	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL is indeterminate.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>T here scores Δ0.33 · evaluated, not missing
Constraint at this position
Conservation	phyloP 12	GERP 1.9, phastCons 1
Regional constraint	o/e 0.85	unconstrained · MANE · 57 kb · p 2.4e-07 · regional, not allelic
Overall
CADD	25.4	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.Glu906Lys
Coding: c.2716G>A
MANE Select: NM_017864
dbSNP: rs2131078812
Type: single nucleotide variant
Location: chr8:94876101 (GRCh38)
Gene constraint: LOEUF 0.453 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 84.47 · 10 PDB
Residue 906: a β-strand

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-glu906lys (accessed [today's date]).

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