Is ILK p.Asp216= (c.648C>T) pathogenic?

ILK p.Asp216= (c.648C>T) is classified Likely benign in ILK (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-03-14). Ultra-rare (popmax 0.0165%, mid); Associated with ILK-related disorder.

What condition is associated with ILK p.Asp216= (c.648C>T)?

ILK p.Asp216= (c.648C>T) is associated with ILK-related disorder (ClinVar).

How common is ILK p.Asp216= (c.648C>T) in the general population?

ILK p.Asp216= (c.648C>T) is ultra-rare (popmax 0.0165%, mid) (gnomAD).

ILK p.Asp216=

c.648C>T · rs1398161503 · VCV3058794

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0165%, mid)

Conditions

ILK-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.38	GERP 1.9, phastCons 0.99
Overall
CADD	9.809	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0165% Middle Eastern · 1/6,062 alleles

Filtering AF 0.00255% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00161%

Overall 0.000684% 10/1,461,852 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0165%	6,062
African / African-American	0.00666%	15,007
European (non-Finnish)	0.000339%	295,005

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: ILK
Protein: p.Asp216=
Coding: c.648C>T
MANE Select: NM_004517
dbSNP: rs1398161503
Type: single nucleotide variant
Location: chr11:6609328 (GRCh38)
Gene constraint: LOEUF 0.798 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 88.13 · 17 PDB
Residue 216: a β-strand; the protein kinase domain

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

Disease context

ILK-related disorder

Similar variants

ILK p.Asp216Gly Uncertain significance ★ ⚠ same residue
ILK p.Asn369fs Uncertain significance ★★ same condition
ILK p.Ala41Val Uncertain significance ★★ ⚠ same type
ILK p.Arg149Gln Uncertain significance ★★ ⚠ same type
ILK p.Arg161Cys Uncertain significance ★★ ⚠ same type
ILK p.Arg161His Uncertain significance ★★ ⚠ same type
ILK p.Arg334Gln Uncertain significance ★★ ⚠ same type
ILK p.Arg436Gln 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/ilk-p-asp216 (accessed [today's date]).

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