Is C6 p.Arg701= (c.2101C>A) pathogenic?

C6 p.Arg701= (c.2101C>A) is classified Likely pathogenic in C6 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-07-18). Very rare (popmax 0.00988%, sas); Associated with complement component 6 deficiency.

What condition is associated with C6 p.Arg701= (c.2101C>A)?

C6 p.Arg701= (c.2101C>A) is associated with complement component 6 deficiency (ClinVar).

How common is C6 p.Arg701= (c.2101C>A) in the general population?

C6 p.Arg701= (c.2101C>A) is very rare (popmax 0.00988%, sas) (gnomAD).

C6 p.Arg701=

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.2101C>A · rs199930769 · VCV2572986

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00988%, sas)

Conditions

complement component 6 deficiency

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>C here scores Δ0.69 · evaluated, not missing
Constraint at this position
Conservation	phyloP 2.3	GERP 0.87, phastCons 1
Overall
CADD	10.71	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00988% South Asian · 9/91,084 alleles

Filtering AF 0.00514% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00375%

Overall 0.00093% 15/1,613,500 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00988%	10,120
Remaining individualsnot grpmax-eligible	0.0064%	15,614
European (non-Finnish)	0.00017%	589,831

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: C6
Protein: p.Arg701=
Coding: c.2101C>A
MANE Select: NM_000065
dbSNP: rs199930769
Type: single nucleotide variant
Location: chr5:41154972 (GRCh38)
Gene constraint: LOEUF 1.008 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 79.72 · 11 PDB
Residue 701: the sushi 1 domain; the 'c5b-binding domain' region; a β-strand; the 'ccp 2' region

Full C6 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

complement component 6 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

C6 p.Arg701Trp Uncertain significance ★★ ⚠ same residue
C6 p.Arg596Ter Pathogenic/Likely pathogenic ★★ same condition
C6 p.Arg606Ter Pathogenic ★★ same condition
C6 p.Cys218Ter Pathogenic/Likely pathogenic ★★ same condition
C6 p.Tyr683Ter Pathogenic/Likely pathogenic ★★ same condition
C6 p.Arg407Cys Uncertain significance ★★ ⚠ same condition
C6 p.Arg48Lys Uncertain significance ★★ ⚠ same condition
C6 p.Asp667His 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/c6-p-arg701 (accessed [today's date]).

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