Is CEP97 p.Ser736fs (c.2206del) pathogenic?

CEP97 p.Ser736fs (c.2206del) is classified Uncertain significance in CEP97 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-08-11). Very rare (popmax 0.000678%, nfe).

How common is CEP97 p.Ser736fs (c.2206del) in the general population?

CEP97 p.Ser736fs (c.2206del) is very rare (popmax 0.000678%, nfe) (gnomAD).

CEP97 p.Ser736fs

c.2206del · rs758638500 · VCV1962138

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.000678%, 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	escapes	premature termination codon in the last exon (11 of 11) — the truncated protein is likely expressed. PVS1 input, not an applied code
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 11	GERP 1.9, phastCons 1
Overall
CADD	28.3	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 0.000678% European (non-Finnish) · 8/1,180,052 alleles

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

Overall 0.000496% 8/1,614,130 alleles · very rare

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: CEP97
Protein: p.Ser736fs
Coding: c.2206del
MANE Select: NM_024548
dbSNP: rs758638500
Type: Deletion
Location: chr3:101765158 (GRCh38)
Gene constraint: LOEUF 0.847 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 58.89
Residue 736: the 'ccp110-binding' region; the 'interaction with mphosph9' region; the 'disordered' region

Full CEP97 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CEP97 p.Ser736= Likely benign ★ same residue
CEP97 p.Ala36fs Uncertain significance ★ same type
CEP97 p.Ile174fs Uncertain significance ★ same type
CEP97 p.Ile238fs Uncertain significance ★ same type
CEP97 p.Ile604_Arg605delinsMet Uncertain significance ★ same type
CEP97 p.Leu718fs Uncertain significance ★ same type
CEP97 p.Ser723fs Uncertain significance ★ same type
CEP97 c.447+14_447+17del Likely benign ★ 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/cep97-p-ser736fs (accessed [today's date]).

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