Is KANK2 p.Pro210Ser (c.628C>T) pathogenic?

KANK2 p.Pro210Ser (c.628C>T) is classified Uncertain significance in KANK2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-07-28). AlphaMissense: likely pathogenic (0.9693); Very rare (popmax 0.00167%, amr); Associated with KANK2-related disorder.

What condition is associated with KANK2 p.Pro210Ser (c.628C>T)?

KANK2 p.Pro210Ser (c.628C>T) is associated with KANK2-related disorder (ClinVar).

How common is KANK2 p.Pro210Ser (c.628C>T) in the general population?

KANK2 p.Pro210Ser (c.628C>T) is very rare (popmax 0.00167%, amr) (gnomAD).

What do computational predictors say about KANK2 p.Pro210Ser (c.628C>T)?

AlphaMissense predicts likely pathogenic (score 0.9693) — an in-silico prediction, not a clinical call.

KANK2 p.Pro210Ser

c.628C>T · rs919408946 · VCV2629359

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9693 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00167%, amr)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

KANK2-related disorder

Computational evidence

Protein change
AlphaMissense	0.9693	likely pathogenic · top 7% in KANK2
REVEL	0.704	pathogenic-leaning
SaProt	LLR -9.83	tolerated
⇒ AlphaMissense and REVEL call this damaging; SaProt does not.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 9.7	GERP 7, phastCons 1
Regional constraint	o/e 0.96	unconstrained · MANE · 28 kb · p 0.16 · regional, not allelic
Overall
CADD	26.4	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

Grpmax group 0.00167% Admixed American · 1/60,002 alleles

Filtering AF 0.000247% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000159%

Overall 0.00062% 10/1,612,062 alleles · very rare exomes 8/1,459,900 · genomes 2/152,162 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00167%	60,002
African / African-American	0.00133%	74,916
South Asian	0.0011%	91,084
European (non-Finnish)	0.000593%	168,567

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.Pro210Ser
Coding: c.628C>T
MANE Select: NM_001136191
dbSNP: rs919408946
Type: single nucleotide variant
Location: chr19:11193452 (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

Disease context

KANK2-related disorder

Similar variants

KANK2 p.Pro210Leu Uncertain significance ★ ⚠ same residue
KANK2 p.Ala157Thr Uncertain significance ⚠ same condition
KANK2 p.Arg642Trp Uncertain significance ⚠ same condition
KANK2 p.Asn679Ser Uncertain significance ⚠ same condition
KANK2 c.1417+9T>C Likely benign same condition
KANK2 c.1521-7T>A Likely benign same condition
KANK2 p.Asn529= Likely benign same condition
KANK2 p.Gly576= Likely benign same condition

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-pro210ser (accessed [today's date]).

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