Is KCND2 p.Arg511Ser (c.1531C>A) pathogenic?

KCND2 p.Arg511Ser (c.1531C>A) is classified Uncertain significance in KCND2 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-10-26). AlphaMissense: likely benign (0.2035); No allele count reported in gnomAD v4.1 (AN 1,613,592); Associated with Inborn genetic diseases.

What condition is associated with KCND2 p.Arg511Ser (c.1531C>A)?

KCND2 p.Arg511Ser (c.1531C>A) is associated with Inborn genetic diseases (ClinVar).

How common is KCND2 p.Arg511Ser (c.1531C>A) in the general population?

KCND2 p.Arg511Ser (c.1531C>A) is no allele count reported in gnomAD v4.1 (AN 1,613,592) (gnomAD).

What do computational predictors say about KCND2 p.Arg511Ser (c.1531C>A)?

AlphaMissense predicts likely benign (score 0.2035) — an in-silico prediction, not a clinical call.

KCND2 p.Arg511Ser

c.1531C>A · rs371278444 · VCV2257264

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2035 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,613,592)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.2035	likely benign
REVEL	0.27	benign-leaning
SaProt	LLR -4.94	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6	GERP 2.1, phastCons 1
Regional constraint	o/e 0.80	unconstrained · MANE · 15 kb · p 0.0014 · regional, not allelic
Overall
CADD	22.4	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

No allele count reported in gnomAD v4.1 (AN 1,613,592). 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: KCND2
Protein: p.Arg511Ser
Coding: c.1531C>A
MANE Select: NM_012281
dbSNP: rs371278444
Type: single nucleotide variant
Location: chr7:120745843 (GRCh38)
Gene constraint: LOEUF 0.428 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 72.28 · 16 PDB
Residue 511: the 'important for normal channel activation and inactivation, for interaction with kcnip2, and probably other family members as well' region

Full KCND2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

KCND2 p.Arg511His Conflicting classifications of pathogenicity ★ ⚠ same residue
KCND2 p.Pro403Leu Pathogenic/Likely pathogenic ★★ same condition
KCND2 p.Val404Met Pathogenic ★★ same condition
KCND2 p.Ala145Thr Uncertain significance ★★ ⚠ same condition
KCND2 p.Arg449Gln Uncertain significance ★★ ⚠ same condition
KCND2 p.Asp150Glu Uncertain significance ★★ same condition
KCND2 p.His77Arg Uncertain significance ★★ ⚠ same condition
KCND2 p.Lys217Arg 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/kcnd2-p-arg511ser (accessed [today's date]).

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