Is INTS8 p.Lys162Gln (c.484A>C) pathogenic?

INTS8 p.Lys162Gln (c.484A>C) is classified Likely benign in INTS8 (ClinVar, No assertion criteria, 1 submitter). AlphaMissense: ambiguous (0.3795); Absent from gnomAD v4.1; Associated with long QT syndrome.

What condition is associated with INTS8 p.Lys162Gln (c.484A>C)?

INTS8 p.Lys162Gln (c.484A>C) is associated with long QT syndrome (ClinVar).

How common is INTS8 p.Lys162Gln (c.484A>C) in the general population?

INTS8 p.Lys162Gln (c.484A>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about INTS8 p.Lys162Gln (c.484A>C)?

AlphaMissense predicts ambiguous (score 0.3795) — an in-silico prediction, not a clinical call.

INTS8 p.Lys162Gln

c.484A>C · rs796052157 · VCV207857

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3795 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense indeterminate

Conditions

long QT syndrome

Computational evidence

Protein change
AlphaMissense	0.3795	ambiguous
REVEL	0.29	benign-leaning
SaProt	LLR -6.20	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense is indeterminate.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 9.1	GERP 0.65, phastCons 1
Regional constraint	o/e 0.85	unconstrained · MANE · 57 kb · p 2.4e-07 · regional, not allelic
Overall
CADD	23.9	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.Lys162Gln
Coding: c.484A>C
MANE Select: NM_017864
dbSNP: rs796052157
Type: single nucleotide variant
Location: chr8:94827759 (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

Disease context

long QT syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

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-lys162gln (accessed [today's date]).

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