Is FCSK p.Glu482= (c.1446G>A) pathogenic?

FCSK p.Glu482= (c.1446G>A) is classified Likely benign in FCSK (ClinVar, Single submitter, 1 submitter; last evaluated 2025-02-17). Absent from gnomAD v4.1.

How common is FCSK p.Glu482= (c.1446G>A) in the general population?

FCSK p.Glu482= (c.1446G>A) is absent from gnomAD v4.1 (gnomAD).

FCSK p.Glu482=

c.1446G>A · rs2507435941 · VCV2024176

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

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 0.36	GERP 0.45, phastCons 0.68
Overall
CADD	0.757	PHRED · no single calibrated threshold — expert panels disagree

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: FCSK
Protein: p.Glu482=
Coding: c.1446G>A
MANE Select: NM_145059
dbSNP: rs2507435941
Type: single nucleotide variant
Location: chr16:70473022 (GRCh38)
Gene constraint: LOEUF 1.254 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 92.20

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

Similar variants

FCSK c.412-2A>G Likely pathogenic ★★ same type
FCSK c.485-2A>G Uncertain significance ★★ same type
FCSK p.Ala297Val Uncertain significance ★★ ⚠ same type
FCSK p.Ala348Ser Uncertain significance ★★ ⚠ same type
FCSK p.Ala481Thr Uncertain significance ★★ ⚠ same type
FCSK p.Ala488Thr Uncertain significance ★★ same type
FCSK p.Ala518Val Uncertain significance ★★ ⚠ same type
FCSK p.Ala554Val 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/fcsk-p-glu482 (accessed [today's date]).

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