Is KANK1 p.Pro69Ser (c.205C>T) pathogenic?

KANK1 p.Pro69Ser (c.205C>T) is classified Uncertain significance in KANK1 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-04-24). AlphaMissense: likely benign (0.0891); Absent from gnomAD v4.1.

How common is KANK1 p.Pro69Ser (c.205C>T) in the general population?

KANK1 p.Pro69Ser (c.205C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about KANK1 p.Pro69Ser (c.205C>T)?

AlphaMissense predicts likely benign (score 0.0891) — an in-silico prediction, not a clinical call.

KANK1 p.Pro69Ser

c.205C>T · rs2539670503 · VCV2130051

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0891 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0891	likely benign
REVEL	0.062	moderately benign-leaning
SaProt	LLR -6.44	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 1.7	GERP 1.6, phastCons 1
Regional constraint	o/e 1.40	unconstrained · MANE · 68 kb · p 3.5e-62 · regional, not allelic
Overall
CADD	13.32	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

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: KANK1
Protein: p.Pro69Ser
Coding: c.205C>T
MANE Select: NM_015158
dbSNP: rs2539670503
Type: single nucleotide variant
Location: chr9:710971 (GRCh38)
Gene constraint: LOEUF 1.149 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 54.50 · 5 PDB
Residue 69: the 'disordered' region

Full KANK1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

KANK1 p.Pro69Leu Benign/Likely benign ★★ same residue
KANK1 p.Pro69Arg Uncertain significance ★ ⚠ same residue
KANK1 p.Pro69= Likely benign ★ same residue
KANK1 c.2896+2T>G Uncertain significance ★★ same type
KANK1 p.Ala109Thr Uncertain significance ★★ ⚠ same type
KANK1 p.Ala1184= Uncertain significance ★★ same type
KANK1 p.Ala1203Val Uncertain significance ★★ ⚠ same type
KANK1 p.Ala1255Asp 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/kank1-p-pro69ser (accessed [today's date]).

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