Is KCND3 p.Pro31= (c.93G>A) pathogenic?

KCND3 p.Pro31= (c.93G>A) is classified Likely benign in KCND3 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-02-02). Very rare (popmax 0.000339%, nfe); Associated with Cardiovascular phenotype.

What condition is associated with KCND3 p.Pro31= (c.93G>A)?

KCND3 p.Pro31= (c.93G>A) is associated with Cardiovascular phenotype (ClinVar).

How common is KCND3 p.Pro31= (c.93G>A) in the general population?

KCND3 p.Pro31= (c.93G>A) is very rare (popmax 0.000339%, nfe) (gnomAD).

KCND3 p.Pro31=

c.93G>A · rs978360186 · VCV1766832

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.000339%, nfe)

Conditions

Cardiovascular phenotype

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 -5.1	GERP -4.2
Overall
CADD	6.391	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000339% European (non-Finnish) · 4/1,179,900 alleles

Filtering AF 7.9e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 5.4e-05%

Overall 0.000248% 4/1,613,762 alleles · very rare exomes 4/1,461,488 · genomes 0/152,274 · 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.Pro31=
Coding: c.93G>A
MANE Select: NM_001378969
dbSNP: rs978360186
Type: single nucleotide variant
Location: chr1:111982634 (GRCh38)
Gene constraint: LOEUF 0.303 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 71.32 · 6 PDB
Residue 31: an α-helix

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.Pro31Ser Uncertain significance ★★ ⚠ same residue
KCND3 p.Pro31Leu Uncertain significance ★ ⚠ same residue
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

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-pro31 (accessed [today's date]).

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