Is KCND3 p.Pro618= (c.1854C>A) pathogenic?

KCND3 p.Pro618= (c.1854C>A) is classified Likely benign in KCND3 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-10-25). Very rare (popmax 0.000169%, nfe); Associated with Cardiovascular phenotype.

What condition is associated with KCND3 p.Pro618= (c.1854C>A)?

KCND3 p.Pro618= (c.1854C>A) is associated with Cardiovascular phenotype (ClinVar).

How common is KCND3 p.Pro618= (c.1854C>A) in the general population?

KCND3 p.Pro618= (c.1854C>A) is very rare (popmax 0.000169%, nfe) (gnomAD).

KCND3 p.Pro618=

c.1854C>A · rs1664100783 · VCV1781381

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.000169%, nfe)

Conditions

Cardiovascular phenotype

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 1.1	GERP -1.5, phastCons 1
Overall
CADD	6.161	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000169% European (non-Finnish) · 2/1,180,052 alleles

Filtering AF 2.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000124% 2/1,614,118 alleles · very rare exomes 1/1,461,880 · genomes 1/152,238 · 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: KCND3
Protein: p.Pro618=
Coding: c.1854C>A
MANE Select: NM_001378969
dbSNP: rs1664100783
Type: single nucleotide variant
Location: chr1:111776191 (GRCh38)
Gene constraint: LOEUF 0.303 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 71.32 · 6 PDB
Residue 618: the 'disordered' region

Full KCND3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Cardiovascular phenotype — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

KCND3 p.Ala144Thr Uncertain significance ★★ ⚠ same condition
KCND3 p.Ala15Val Uncertain significance ★★ ⚠ same condition
KCND3 p.Ala172Thr Uncertain significance ★★ ⚠ same condition
KCND3 p.Ala30Asp Uncertain significance ★★ ⚠ same condition
KCND3 p.Ala348Val Uncertain significance ★★ ⚠ same condition
KCND3 p.Ala654Thr Uncertain significance ★★ ⚠ same condition
KCND3 p.Arg13Gln Uncertain significance ★★ ⚠ same condition
KCND3 p.Arg293His Uncertain significance ★★ ⚠ 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/kcnd3-p-pro618 (accessed [today's date]).

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