Is KCNA7 p.Arg287Cys (c.859C>T) pathogenic?

KCNA7 p.Arg287Cys (c.859C>T) is classified Uncertain significance in KCNA7 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-06-07). AlphaMissense: likely pathogenic (0.9745); Very rare (popmax 0.00458%, nfe).

How common is KCNA7 p.Arg287Cys (c.859C>T) in the general population?

KCNA7 p.Arg287Cys (c.859C>T) is very rare (popmax 0.00458%, nfe) (gnomAD).

What do computational predictors say about KCNA7 p.Arg287Cys (c.859C>T)?

AlphaMissense predicts likely pathogenic (score 0.9745) — an in-silico prediction, not a clinical call.

KCNA7 p.Arg287Cys

c.859C>T · VCV4041415

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9745 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00458%, nfe)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9745	likely pathogenic
REVEL	0.958	strongly pathogenic-leaning
SaProt	LLR -13.70	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 10	phastCons 1
Regional constraint	o/e 0.98	unconstrained · MANE · 2,519 bp · p 0.65 · regional, not allelic
Overall
CADD	34.0	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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

Grpmax group 0.00458% European (non-Finnish) · 54/1,180,050 alleles

Filtering AF 0.00358% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00321%

Overall 0.00397% 64/1,614,080 alleles · very rare exomes 60/1,461,862 · genomes 4/152,218 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00458%	21,853
South Asian	0.00439%	22,773
Finnishnot grpmax-eligible	0.00312%	32,009
African / African-American	0.00267%	37,464
Admixed American	0.00167%	60,004
Remaining individualsnot grpmax-eligible	0.0016%	62,488

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: KCNA7
Protein: p.Arg287Cys
Coding: c.859C>T
MANE Select: NM_031886
Type: single nucleotide variant
Location: chr19:49070575 (GRCh38)
Gene constraint: LOEUF 1.237 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 82.12

Full KCNA7 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

KCNA7 p.Arg287His Uncertain significance ★ ⚠ same residue
KCNA7 p.Ala141Thr Uncertain significance ★ ⚠ same type
KCNA7 p.Ala178Asp Uncertain significance ★ ⚠ same type
KCNA7 p.Ala182Thr Uncertain significance ★ ⚠ same type
KCNA7 p.Ala188Thr Uncertain significance ★ ⚠ same type
KCNA7 p.Ala188Val Uncertain significance ★ ⚠ same type
KCNA7 p.Ala235Val Uncertain significance ★ ⚠ same type
KCNA7 p.Ala275Thr Uncertain significance ★ ⚠ same type

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/kcna7-p-arg287cys (accessed [today's date]).

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