Is C7 p.Leu286fs (c.856_857del) pathogenic?

C7 p.Leu286fs (c.856857del) is classified Pathogenic in C7 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-01-24). Very rare (popmax 0.00167%, amr).

How common is C7 p.Leu286fs (c.856_857del) in the general population?

C7 p.Leu286fs (c.856_857del) is very rare (popmax 0.00167%, amr) (gnomAD).

C7 p.Leu286fs

c.856_857del · VCV3646284

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00167%, amr)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function; NMD-escape possible for C-terminal truncations
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 5.9	GERP 2.4, phastCons 1
Overall
CADD	23.9	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00167% Admixed American · 1/59,950 alleles

Overall 0.000657% 1/152,100 alleles · very rare

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: C7
Protein: p.Leu286fs
Coding: c.856_857del
MANE Select: NM_001565 · reported on NM_000587
Type: Microsatellite
Location: chr5:40947715 (GRCh38)
Structure: AlphaFold pLDDT 89.67 · 6 PDB

Full C7 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

C7 p.His643fs Pathogenic ★★ same type
C7 c.2166-1_2166insGCTGGGCGCGGTGGCTCACGCCTGTAATCCCAGCACTTTGGGAGGCCGAGGTGGGCGGATCACGAGGTCAGGAGATCGAGACCATACTGNNNNNNNNNNAAAAAAAAAAAAAAAAAAAAAAAAATTCTTTTCAG Pathogenic ★ same type
C7 p.Glu615del Uncertain significance ★ same type
C7 p.Pro135del Uncertain significance ★ same type
C7 p.Ser232del Uncertain significance ★ same type
C7 c.*96TCT[1] Benign ★ same type
C7 p.Val714fs Pathogenic 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/c7-p-leu286fs (accessed [today's date]).

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