Is C8B p.Cys24fs (c.71_74del) pathogenic?

C8B p.Cys24fs (c.7174del) is classified Pathogenic in C8B (ClinVar, Single submitter, 1 submitter; last evaluated 2024-07-31). Very rare (popmax 0.000593%, nfe).

How common is C8B p.Cys24fs (c.71_74del) in the general population?

C8B p.Cys24fs (c.71_74del) is very rare (popmax 0.000593%, nfe) (gnomAD).

C8B p.Cys24fs

c.71_74del · rs780667562 · VCV1959060

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.000593%, nfe)

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 1 of 12
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 0.65	GERP 0.41, phastCons 0.094
Overall
CADD	33.0	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 0.000593% European (non-Finnish) · 7/1,180,038 alleles

Filtering AF 0.000247% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000159%

Overall 0.00062% 10/1,614,010 alleles · very rare

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	0.00312%	32,011
Remaining individualsnot grpmax-eligible	0.0016%	62,486
European (non-Finnish)grpmax	0.000593%	168,577

Finnish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Cys24fs
Coding: c.71_74del
MANE Select: NM_000066
dbSNP: rs780667562
Type: Deletion
Location: chr1:56965875 (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

Similar variants

C8B p.Cys24Tyr Uncertain significance ★ ⚠ same residue
C8B p.Cys24= Likely benign ★ same residue
C8B p.Phe47fs Pathogenic/Likely pathogenic ★★ same type
C8B p.Asn113fs Pathogenic ★ same type
C8B p.Asn184fs Pathogenic ★ same type
C8B p.Glu66fs Pathogenic ★ same type
C8B p.Leu18fs Pathogenic ★ same type
C8B p.Leu372fs 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-cys24fs (accessed [today's date]).

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