Is C6 p.Asp565= (c.1695C>T) pathogenic?

C6 p.Asp565= (c.1695C>T) is classified Benign/Likely benign in C6 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2026-01-26). Common (popmax 5.72%, eas) — too common for a highly-penetrant pathogenic allele; Associated with complement component 6 deficiency.

What condition is associated with C6 p.Asp565= (c.1695C>T)?

C6 p.Asp565= (c.1695C>T) is associated with complement component 6 deficiency (ClinVar).

C6 p.Asp565=

Q: How common is C6 p.Asp565= (c.1695C>T) in the general population?

C6 p.Asp565= (c.1695C>T) is common (popmax 5.72%, eas) — too common for a highly-penetrant pathogenic allele (gnomAD).

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.1695C>T · rs79523005 · VCV1167259

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Common

common (popmax 5.72%, eas) — too common for a highly-penetrant pathogenic allele

Conditions

complement component 6 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 -3.7, phastCons 0.003
Overall
CADD	7.515	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 5.72% East Asian · 2,560/44,744 alleles

Filtering AF 5.54% ClinGen BA1/BS1 input FAF95, joint · FAF99 5.46%

Overall 0.186% 2,998/1,612,896 alleles · common

Ancestry group	Frequency	1 in
East Asiangrpmax	5.72%	17
African / African-American	0.27%	371
Remaining individualsnot grpmax-eligible	0.242%	414
Admixed American	0.0234%	4,276
South Asian	0.022%	4,551
European (non-Finnish)	0.00432%	23,126

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.Asp565=
Coding: c.1695C>T
MANE Select: NM_000065
dbSNP: rs79523005
Type: single nucleotide variant
Location: chr5:41159243 (GRCh38)
Gene constraint: LOEUF 1.008 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 79.72 · 11 PDB
Residue 565: a disulfide bond; the tsp type-1 3 domain

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.Asp565His 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.Arg701Trp 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-asp565 (accessed [today's date]).

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