Is C7 p.Glu447= (c.1341G>A) pathogenic?

C7 p.Glu447= (c.1341G>A) is classified Benign/Likely benign in C7 (ClinVar, Multiple submitters, 7 submitters; last evaluated 2026-04-01). Rare (popmax 0.907%, mid); Associated with complement component 7 deficiency.

What condition is associated with C7 p.Glu447= (c.1341G>A)?

C7 p.Glu447= (c.1341G>A) is associated with complement component 7 deficiency (ClinVar).

How common is C7 p.Glu447= (c.1341G>A) in the general population?

C7 p.Glu447= (c.1341G>A) is rare (popmax 0.907%, mid) (gnomAD).

C7 p.Glu447=

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.1341G>A · rs150696042 · VCV1166124

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 7 submitters

gnomAD v4.1

Rare

rare (popmax 0.907%, mid)

Conditions

complement component 7 deficiency

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.13	GERP -4.1, phastCons 0.6
Overall
CADD	3.564	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.907% Middle Eastern · 55/6,062 alleles

Filtering AF 0.716% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.647%

Overall 0.183% 2,961/1,613,842 alleles · rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.907%	110
Remaining individualsnot grpmax-eligible	0.224%	446
European (non-Finnish)	0.201%	498
Admixed American	0.19%	526
Ashkenazi Jewishnot grpmax-eligible	0.152%	658
South Asian	0.132%	759
Finnishnot grpmax-eligible	0.111%	902
Amishnot grpmax-eligible	0.11%	912
African / African-American	0.0587%	1,705

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.Glu447=
Coding: c.1341G>A
MANE Select: NM_001565 · reported on NM_000587
dbSNP: rs150696042
Type: single nucleotide variant
Location: chr5:40958113 (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 c.281-1G>T Pathogenic/Likely pathogenic ★★ same condition
C7 c.63-1G>A Pathogenic ★★ same condition
C7 p.Gly379Arg Pathogenic/Likely pathogenic ★★ ⚠ same condition
C7 p.Trp205Ter Pathogenic/Likely pathogenic ★★ same condition
C7 p.Arg220Gln Uncertain significance ★★ ⚠ same condition
C7 p.Arg402Gln Uncertain significance ★★ ⚠ same condition
C7 p.Arg618Trp Uncertain significance ★★ ⚠ same condition
C7 p.Asn202Ser Uncertain significance ★★ ⚠ 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-glu447 (accessed [today's date]).

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