Is KANK4 p.Ser809Pro (c.2425T>C) pathogenic?

KANK4 p.Ser809Pro (c.2425T>C) is classified Uncertain significance in KANK4 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-06-12). AlphaMissense: likely benign (0.2263); Absent from gnomAD v4.1.

How common is KANK4 p.Ser809Pro (c.2425T>C) in the general population?

KANK4 p.Ser809Pro (c.2425T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about KANK4 p.Ser809Pro (c.2425T>C)?

AlphaMissense predicts likely benign (score 0.2263) — an in-silico prediction, not a clinical call.

KANK4 p.Ser809Pro

c.2425T>C · VCV4041059

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2263 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2263	likely benign
REVEL	0.141	moderately benign-leaning
SaProt	LLR -10.91	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 2.2	GERP 0.32, phastCons 0.78
Regional constraint	o/e 0.98	unconstrained · MANE · 37 kb · p 0.46 · regional, not allelic
Overall
CADD	23.0	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: KANK4
Protein: p.Ser809Pro
Coding: c.2425T>C
MANE Select: NM_181712
Type: single nucleotide variant
Location: chr1:62263206 (GRCh38)
Gene constraint: LOEUF 0.829 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 57.17

Full KANK4 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

KANK4 p.Ala115Val Uncertain significance ★★ ⚠ same type
KANK4 p.Ala987Thr Uncertain significance ★★ ⚠ same type
KANK4 p.Arg336Met Uncertain significance ★★ ⚠ same type
KANK4 p.Arg471Cys Uncertain significance ★★ ⚠ same type
KANK4 p.Arg653Cys Uncertain significance ★★ ⚠ same type
KANK4 p.Arg790Gln Uncertain significance ★★ ⚠ same type
KANK4 p.Asp266Gly Uncertain significance ★★ ⚠ same type
KANK4 p.Asp459Val 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/kank4-p-ser809pro (accessed [today's date]).

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