Is KCNH2 p.Pro596= (c.1788C>G) pathogenic?

KCNH2 p.Pro596= (c.1788C>G) is classified Likely benign in KCNH2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2023-10-13). Absent from gnomAD v4.1; Associated with long QT syndrome.

What condition is associated with KCNH2 p.Pro596= (c.1788C>G)?

KCNH2 p.Pro596= (c.1788C>G) is associated with long QT syndrome (ClinVar).

How common is KCNH2 p.Pro596= (c.1788C>G) in the general population?

KCNH2 p.Pro596= (c.1788C>G) is absent from gnomAD v4.1 (gnomAD).

KCNH2 p.Pro596=

c.1788C>G · rs1801166919 · VCV1082910

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

long QT syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.01	GERP -3.8, phastCons 0.52
Overall
CADD	7.315	PHRED · no single calibrated threshold — expert panels disagree

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: KCNH2
Protein: p.Pro596=
Coding: c.1788C>G
MANE Select: NM_000238
dbSNP: rs1801166919
Type: single nucleotide variant
Location: chr7:150951605 (GRCh38)
Gene constraint: LOEUF 0.568 · pLI 0.07 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 63.94 · 24 PDB
Residue 596: a UniProt-annotated variant site (in lqt2; uncertain significance); a UniProt-annotated variant site (in lqt2)

Full KCNH2 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

KCNH2 p.Pro596Ala Pathogenic ★ ⚠ same residue
KCNH2 p.Pro596His Pathogenic ★ ⚠ same residue
KCNH2 c.1129-1G>A Pathogenic ★★ same condition
KCNH2 c.1129-2A>G Pathogenic ★★ same condition
KCNH2 c.1557+1G>C Pathogenic/Likely pathogenic ★★ same condition
KCNH2 c.1945+1G>A Likely pathogenic ★★ same condition
KCNH2 c.1945+6T>C Pathogenic/Likely pathogenic ★★ same condition
KCNH2 c.1946-2A>C Pathogenic ★★ same condition

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/kcnh2-p-pro596 (accessed [today's date]).

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