Is C8B p.Cys116Ter (c.348C>A) pathogenic?

C8B p.Cys116Ter (c.348C>A) is classified Pathogenic in C8B (ClinVar, Single submitter, 1 submitter; last evaluated 2019-09-10). Very rare (popmax 8.47e-05%, nfe); Associated with type II complement component 8 deficiency.

What condition is associated with C8B p.Cys116Ter (c.348C>A)?

C8B p.Cys116Ter (c.348C>A) is associated with type II complement component 8 deficiency (ClinVar).

How common is C8B p.Cys116Ter (c.348C>A) in the general population?

C8B p.Cys116Ter (c.348C>A) is very rare (popmax 8.47e-05%, nfe) (gnomAD).

C8B p.Cys116Ter

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.348C>A · rs753002884 · VCV1325387

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 8.47e-05%, nfe)

Conditions

type II complement component 8 deficiency

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function
NMD	predicted	premature termination codon in exon 3 of 12
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.4	GERP 0.33, phastCons 1
Overall
CADD	37.0	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 8.47e-05% European (non-Finnish) · 1/1,179,976 alleles

Overall 6.2e-05% 1/1,613,998 alleles · very rare exomes 1/1,461,804 · genomes 0/152,194 · 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: C8B
Protein: p.Cys116Ter
Coding: c.348C>A
MANE Select: NM_000066
dbSNP: rs753002884
Type: single nucleotide variant
Location: chr1:56956812 (GRCh38)
Gene constraint: LOEUF 1.18 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.99 · 8 PDB
Residue 116: a disulfide bond; a UniProt-annotated variant site (in c8d2); the tsp type-1 1 domain

Full C8B gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

type II complement component 8 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

C8B p.Arg284Ter Pathogenic ★★ same condition
C8B p.Arg428Ter Pathogenic ★★ same condition
C8B p.Gln91Ter Pathogenic/Likely pathogenic ★★ same condition
C8B p.Trp9Ter Pathogenic ★★ same condition
C8B p.Ala461Ser Uncertain significance ★★ ⚠ same condition
C8B p.Ala480Thr Uncertain significance ★★ ⚠ same condition
C8B p.Arg136His Uncertain significance ★★ ⚠ same condition
C8B p.Arg323Trp 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/c8b-p-cys116ter (accessed [today's date]).

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