Is C9 p.Ser263fs (c.787del) pathogenic?

C9 p.Ser263fs (c.787del) is classified Pathogenic in C9 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-02-20). Very rare (popmax 0.00134%, afr).

How common is C9 p.Ser263fs (c.787del) in the general population?

C9 p.Ser263fs (c.787del) is very rare (popmax 0.00134%, afr) (gnomAD).

C9 p.Ser263fs

c.787del · rs1357217922 · VCV1074589

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00134%, 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 6 of 11
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 0.003	GERP -2.8
Overall
CADD	15.79	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 0.00134% African / African-American · 1/74,860 alleles

Filtering AF 6.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.9e-05%

Overall 0.000248% 4/1,612,356 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00134%	74,860
European (non-Finnish)	0.000255%	392,886

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: C9
Protein: p.Ser263fs
Coding: c.787del
MANE Select: NM_001737
dbSNP: rs1357217922
Type: Deletion
Location: chr5:39315858 (GRCh38)
Gene constraint: LOEUF 1.223 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 79.32 · 9 PDB
Residue 263: the macpf domain

Full C9 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

C9 p.Ser263Ala Uncertain significance ★ ⚠ same residue
C9 p.Asp403fs Pathogenic/Likely pathogenic ★★ same type
C9 p.Met293fs Pathogenic/Likely pathogenic ★★ same type
C9 p.Ser240_Leu241insTer Pathogenic/Likely pathogenic ★★ same type
C9 p.Tyr193fs Pathogenic/Likely pathogenic ★★ same type
C9 p.Lys559fs Uncertain significance ★★ same type
C9 p.Arg139fs Pathogenic ★ same type
C9 p.Glu149_Ser150insTer 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/c9-p-ser263fs (accessed [today's date]).

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