Is C6 p.Ser311= (c.933T>C) pathogenic?

C6 p.Ser311= (c.933T>C) is classified Benign/Likely benign in C6 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2026-01-26). Common (popmax 5.73%, eas) — too common for a highly-penetrant pathogenic allele; Associated with complement component 6 deficiency.

What condition is associated with C6 p.Ser311= (c.933T>C)?

C6 p.Ser311= (c.933T>C) is associated with complement component 6 deficiency (ClinVar).

C6 p.Ser311=

Q: How common is C6 p.Ser311= (c.933T>C) in the general population?

C6 p.Ser311= (c.933T>C) is common (popmax 5.73%, 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.933T>C · rs75043846 · VCV1167260

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Common

common (popmax 5.73%, 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 0.38	GERP -2.4, phastCons 0.7
Overall
CADD	5.627	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 5.73% East Asian · 2,562/44,742 alleles

Filtering AF 5.54% ClinGen BA1/BS1 input FAF95, joint · FAF99 5.47%

Overall 0.17% 2,733/1,610,564 alleles · common exomes 2,522/1,458,206 · genomes 211/152,358 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	5.73%	17
Remaining individualsnot grpmax-eligible	0.2%	499
South Asian	0.0187%	5,348
Admixed American	0.0167%	5,997
African / African-American	0.004%	24,997
European (non-Finnish)	0.00136%	73,606

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.Ser311=
Coding: c.933T>C
MANE Select: NM_000065
dbSNP: rs75043846
Type: single nucleotide variant
Location: chr5:41176710 (GRCh38)
Gene constraint: LOEUF 1.008 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 79.72 · 11 PDB
Residue 311: a β-strand; the macpf 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.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
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-ser311 (accessed [today's date]).

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