Is KANK2 p.Pro534= (c.1602G>A) pathogenic?

KANK2 p.Pro534= (c.1602G>A) is classified Benign/Likely benign in KANK2 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2026-01-27). Low-frequency (popmax 1.21%, sas).

How common is KANK2 p.Pro534= (c.1602G>A) in the general population?

KANK2 p.Pro534= (c.1602G>A) is low-frequency (popmax 1.21%, sas) (gnomAD).

KANK2 p.Pro534=

c.1602G>A · rs61734799 · VCV782052

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

low-frequency (popmax 1.21%, sas)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -11	GERP -4.6
Overall
CADD	0.206	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 1.21% South Asian · 1,091/90,514 alleles

Filtering AF 1.15% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.12%

Overall 0.722% 11,625/1,609,678 alleles · low-frequency exomes 10,908/1,457,374 · genomes 717/152,304 · joint denominator

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	1.46%	69
South Asiangrpmax	1.21%	83
Middle Eastern	0.991%	101
Remaining individualsnot grpmax-eligible	0.814%	123
European (non-Finnish)	0.778%	128
Admixed American	0.32%	313
African / African-American	0.171%	586
Finnishnot grpmax-eligible	0.0861%	1,161

Ashkenazi Jewish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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: KANK2
Protein: p.Pro534=
Coding: c.1602G>A
MANE Select: NM_001136191
dbSNP: rs61734799
Type: single nucleotide variant
Location: chr19:11176736 (GRCh38)
Gene constraint: LOEUF 0.704 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 60.58 · 3 PDB
Residue 534: the 'disordered' region

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

Similar variants

KANK2 p.Pro534Leu Uncertain significance ★ ⚠ same residue
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

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-pro534 (accessed [today's date]).

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