Is C7 p.Val714fs (c.2140_2141del) pathogenic?

C7 p.Val714fs (c.21402141del) is classified Pathogenic in C7 (ClinVar, No assertion criteria, 1 submitter; last evaluated 1996-11-01). Ultra-rare (popmax 0.029%, eas); Associated with complement component 7 deficiency.

What condition is associated with C7 p.Val714fs (c.2140_2141del)?

C7 p.Val714fs (c.2140_2141del) is associated with complement component 7 deficiency (ClinVar).

How common is C7 p.Val714fs (c.2140_2141del) in the general population?

C7 p.Val714fs (c.2140_2141del) is ultra-rare (popmax 0.029%, eas) (gnomAD).

C7 p.Val714fs

Q: How is Immunodeficiency due to a late component of complement deficiency inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

c.2140_2141del · rs1467298230 · VCV12104

Pathogenic No assertion criteria

Classification

Pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

ultra-rare (popmax 0.029%, eas)

Conditions

complement component 7 deficiency

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 5.1	GERP 0.33, phastCons 1
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 0.029% East Asian · 13/44,768 alleles

Filtering AF 0.0171% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0136%

Overall 0.000809% 13/1,607,046 alleles · ultra-rare exomes 12/1,454,888 · genomes 1/152,158 · joint denominator

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.Val714fs
Coding: c.2140_2141del
MANE Select: NM_000587
dbSNP: rs1467298230
Type: Microsatellite
Location: chr5:40976812 (GRCh38)
Structure: AlphaFold pLDDT 89.67 · 6 PDB

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

Disease context

complement component 7 deficiency — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Immunodeficiency due to a late component of complement deficiency (Orphanet):

Inheritance: Autosomal recessive

Similar variants

C7 p.His643fs Pathogenic ★★ same condition
C7 c.*96TCT[1] Benign ★ same condition
C7 c.2350+1del Likely pathogenic ★★ same condition
C7 c.281-1G>T Pathogenic/Likely pathogenic ★★ same condition
C7 c.63-1G>A Pathogenic ★★ same condition
C7 p.Asn136fs Pathogenic/Likely pathogenic ★★ same condition
C7 p.Gly379Arg Pathogenic/Likely pathogenic ★★ same condition
C7 p.Ser212fs Pathogenic/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-val714fs (accessed [today's date]).

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