Is C7 p.Cys455fs (c.1362_1363del) pathogenic?

C7 p.Cys455fs (c.13621363del) is classified Pathogenic in C7 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-06-19). Ultra-rare (popmax 0.0134%, eas).

How common is C7 p.Cys455fs (c.1362_1363del) in the general population?

C7 p.Cys455fs (c.1362_1363del) is ultra-rare (popmax 0.0134%, eas) (gnomAD).

C7 p.Cys455fs

c.1362_1363del · VCV3696725

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

ultra-rare (popmax 0.0134%, eas)

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 3.7	GERP -0.25, phastCons 0.95
Overall
CADD	34.0	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 0.0134% East Asian · 6/44,880 alleles

Filtering AF 0.00579% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00394%

Overall 0.000434% 7/1,613,666 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0134%	7,480
European (non-Finnish)	8.48e-05%	1,179,782

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.Cys455fs
Coding: c.1362_1363del
MANE Select: NM_001565 · reported on NM_000587
Type: Deletion
Location: chr5:40958134 (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 c.2350+1del Likely pathogenic ★★ same type
C7 p.Asn136fs Pathogenic/Likely pathogenic ★★ same type
C7 p.Cys85fs Pathogenic/Likely pathogenic ★★ same type
C7 p.Ser212fs Pathogenic/Likely pathogenic ★★ same type
C7 p.Ala363fs Pathogenic ★ same type
C7 p.Ala698fs Pathogenic ★ same type
C7 p.Arg294fs Pathogenic ★ same type
C7 p.Asn157fs 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-cys455fs (accessed [today's date]).

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