Is C8B p.Phe47fs (c.138del) pathogenic?

C8B p.Phe47fs (c.138del) is classified Pathogenic/Likely pathogenic in C8B (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-03-17). Very rare (popmax 0.00167%, amr); Associated with type II complement component 8 deficiency.

What condition is associated with C8B p.Phe47fs (c.138del)?

C8B p.Phe47fs (c.138del) is associated with type II complement component 8 deficiency (ClinVar).

How common is C8B p.Phe47fs (c.138del) in the general population?

C8B p.Phe47fs (c.138del) is very rare (popmax 0.00167%, amr) (gnomAD).

C8B p.Phe47fs

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.138del · rs779205550 · VCV2174163

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00167%, amr)

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	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 2 of 12
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 1.4	GERP -2.2, phastCons 1
Overall
CADD	27.5	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 0.00167% Admixed American · 1/60,004 alleles

Filtering AF 7.9e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 5.4e-05%

Overall 0.00031% 5/1,614,054 alleles · very rare exomes 4/1,461,858 · genomes 1/152,196 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00167%	60,004
European (non-Finnish)	0.000339%	295,004

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.Phe47fs
Coding: c.138del
MANE Select: NM_000066
dbSNP: rs779205550
Type: Deletion
Location: chr1:56960131 (GRCh38)
Gene constraint: LOEUF 1.18 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.99 · 8 PDB

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.Asn113fs Pathogenic ★ same condition
C8B p.Pro202fs Pathogenic same condition
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

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-phe47fs (accessed [today's date]).

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