Is ILK p.Leu320Phe (c.958C>T) pathogenic?

ILK p.Leu320Phe (c.958C>T) is classified Uncertain significance in ILK (ClinVar, Single submitter, 1 submitter; last evaluated 2023-05-09). AlphaMissense: likely pathogenic (0.5799); Absent from gnomAD v4.1; Associated with familial hypertrophic cardiomyopathy.

What condition is associated with ILK p.Leu320Phe (c.958C>T)?

ILK p.Leu320Phe (c.958C>T) is associated with familial hypertrophic cardiomyopathy (ClinVar).

How common is ILK p.Leu320Phe (c.958C>T) in the general population?

ILK p.Leu320Phe (c.958C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ILK p.Leu320Phe (c.958C>T)?

AlphaMissense predicts likely pathogenic (score 0.5799) — an in-silico prediction, not a clinical call.

ILK p.Leu320Phe

c.958C>T · rs912510389 · VCV2807874

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.5799 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

familial hypertrophic cardiomyopathy

Computational evidence

Protein change
AlphaMissense	0.5799	likely pathogenic
REVEL	0.923	moderately pathogenic-leaning
SaProt	LLR -8.63	tolerated
⇒ AlphaMissense and REVEL call this damaging; SaProt does not.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 4.9	GERP 0.89, phastCons 1
Regional constraint	o/e 0.89	unconstrained · MANE · 6,336 bp · p 0.0056 · regional, not allelic
Overall
CADD	24.3	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: ILK
Protein: p.Leu320Phe
Coding: c.958C>T
MANE Select: NM_006284 · reported on NM_004517
dbSNP: rs912510389
Type: single nucleotide variant
Location: chr11:6609825 (GRCh38)

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

Disease context

familial hypertrophic cardiomyopathy — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

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-leu320phe (accessed [today's date]).

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