Is C7 p.Cys85fs (c.253del) pathogenic?

C7 p.Cys85fs (c.253del) is classified Pathogenic/Likely pathogenic in C7 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2026-01-14). Very rare (popmax 0.005%, amr); Associated with C7-related disorders.

What condition is associated with C7 p.Cys85fs (c.253del)?

C7 p.Cys85fs (c.253del) is associated with C7-related disorders (ClinVar).

How common is C7 p.Cys85fs (c.253del) in the general population?

C7 p.Cys85fs (c.253del) is very rare (popmax 0.005%, amr) (gnomAD).

C7 p.Cys85fs

c.253del · rs769923441 · VCV1992071

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.005%, amr)

Conditions

C7-related disorders

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 -0.33	GERP -4.4, phastCons 0.007
Overall
CADD	32.0	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 0.005% Admixed American · 3/59,972 alleles

Filtering AF 0.00133% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0009%

Overall 0.00143% 23/1,613,616 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.005%	19,991
European (non-Finnish)	0.0017%	58,986

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.Cys85fs
Coding: c.253del
MANE Select: NM_001565 · reported on NM_000587
dbSNP: rs769923441
Type: Deletion
Location: chr5:40934439 (GRCh38)
Structure: AlphaFold pLDDT 89.67 · 6 PDB
Residue 85: an α-helix

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

Disease context

C7-related disorders

Similar variants

C7 p.Asn136fs Pathogenic/Likely pathogenic ★★ same condition
C7 p.Ser212fs Pathogenic/Likely pathogenic ★★ same condition
C7 c.739-2A>G Likely pathogenic ★★ same condition
C7 p.Arg402Ter Pathogenic/Likely pathogenic ★★ same condition
C7 p.Gly379Arg Pathogenic/Likely pathogenic ★★ ⚠ same condition
C7 p.Asn494Lys Uncertain significance ★★ ⚠ same condition
C7 c.2166-1G>A Likely pathogenic ★ same condition
C7 c.982+2T>C Likely pathogenic ★ same condition

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-cys85fs (accessed [today's date]).

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