Is KCNH2 p.Ser992= (c.2976A>G) pathogenic?

KCNH2 p.Ser992= (c.2976A>G) is classified Likely benign in KCNH2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-09-29). No allele count reported in gnomAD v4.1 (AN 1,591,200); Associated with long QT syndrome.

What condition is associated with KCNH2 p.Ser992= (c.2976A>G)?

KCNH2 p.Ser992= (c.2976A>G) is associated with long QT syndrome (ClinVar).

How common is KCNH2 p.Ser992= (c.2976A>G) in the general population?

KCNH2 p.Ser992= (c.2976A>G) is no allele count reported in gnomAD v4.1 (AN 1,591,200) (gnomAD).

KCNH2 p.Ser992=

c.2976A>G · rs2116930515 · VCV1638081

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,591,200)

Conditions

long QT syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Splicing
SpliceAI	Δ0.43	acceptor loss, 21 bp away · masked 0 · deltas
Constraint at this position
Conservation	phyloP -6	GERP -2.7
Overall
CADD	0.86	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

No allele count reported in gnomAD v4.1 (AN 1,591,200). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: KCNH2
Protein: p.Ser992=
Coding: c.2976A>G
MANE Select: NM_000238
dbSNP: rs2116930515
Type: single nucleotide variant
Location: chr7:150947504 (GRCh38)
Gene constraint: LOEUF 0.568 · pLI 0.07 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 63.94 · 24 PDB

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.Ser992Ala Uncertain significance ★ ⚠ 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
KCNH2 c.2145+1G>A Pathogenic/Likely 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-ser992 (accessed [today's date]).

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