Is C8B p.Asn184fs (c.550_553del) pathogenic?

C8B p.Asn184fs (c.550553del) is classified Pathogenic in C8B (ClinVar, Single submitter, 1 submitter; last evaluated 2025-02-12). Very rare (popmax 0.00133%, afr).

How common is C8B p.Asn184fs (c.550_553del) in the general population?

C8B p.Asn184fs (c.550_553del) is very rare (popmax 0.00133%, afr) (gnomAD).

C8B p.Asn184fs

c.550_553del · rs1464732473 · VCV1453762

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00133%, afr)

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 5 of 12
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -0.36	GERP -4.6
Overall
CADD	29.9	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 0.00133% African / African-American · 1/74,942 alleles

Filtering AF 0.000292% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000211%

Overall 0.000558% 9/1,614,072 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00133%	74,942
European (non-Finnish)	0.000678%	147,502

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.Asn184fs
Coding: c.550_553del
MANE Select: NM_000066
dbSNP: rs1464732473
Type: Deletion
Location: chr1:56952161 (GRCh38)
Gene constraint: LOEUF 1.18 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.99 · 8 PDB
Residue 184: a disulfide bond; a UniProt-annotated variant site (in c8d2); the macpf domain

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

Similar variants

C8B p.Asn184= Likely benign ★ same residue
C8B p.Phe47fs Pathogenic/Likely pathogenic ★★ same type
C8B p.Asn113fs Pathogenic ★ same type
C8B p.Cys24fs Pathogenic ★ same type
C8B p.Glu66fs Pathogenic ★ same type
C8B p.Leu18fs Pathogenic ★ same type
C8B p.Leu372fs Pathogenic ★ same type
C8B p.Met248fs Pathogenic ★ same type

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-asn184fs (accessed [today's date]).

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