Is KANK2 p.Ala91Pro (c.271G>C) pathogenic?

KANK2 p.Ala91Pro (c.271G>C) is classified Uncertain significance in KANK2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-01-10). AlphaMissense: ambiguous (0.4141); Absent from gnomAD v4.1.

How common is KANK2 p.Ala91Pro (c.271G>C) in the general population?

KANK2 p.Ala91Pro (c.271G>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about KANK2 p.Ala91Pro (c.271G>C)?

AlphaMissense predicts ambiguous (score 0.4141) — an in-silico prediction, not a clinical call.

KANK2 p.Ala91Pro

c.271G>C · rs1039934970 · VCV2760357

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4141 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense indeterminate

Computational evidence

Protein change
AlphaMissense	0.4141	ambiguous
REVEL	0.075	moderately benign-leaning
SaProt	LLR -7.67	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense is indeterminate.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 4.7	GERP 5.4, phastCons 1
Regional constraint	o/e 0.96	unconstrained · MANE · 28 kb · p 0.16 · regional, not allelic
Overall
CADD	23.5	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: KANK2
Protein: p.Ala91Pro
Coding: c.271G>C
MANE Select: NM_001136191
dbSNP: rs1039934970
Type: single nucleotide variant
Location: chr19:11193809 (GRCh38)
Gene constraint: LOEUF 0.704 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 60.58 · 3 PDB

Full KANK2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

KANK2 p.Ala182Val Uncertain significance ★★ ⚠ same type
KANK2 p.Ala317Val Uncertain significance ★★ ⚠ same type
KANK2 p.Ala347Thr Uncertain significance ★★ ⚠ same type
KANK2 p.Ala351Thr Uncertain significance ★★ ⚠ same type
KANK2 p.Ala393Gly Uncertain significance ★★ ⚠ same type
KANK2 p.Ala653Val Uncertain significance ★★ ⚠ same type
KANK2 p.Ala711Val Uncertain significance ★★ same type
KANK2 p.Arg105His 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/kank2-p-ala91pro (accessed [today's date]).

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