Is CEP97 p.Ser701Phe (c.2102C>T) pathogenic?

CEP97 p.Ser701Phe (c.2102C>T) is classified Uncertain significance in CEP97 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-12-01). AlphaMissense: likely pathogenic (0.7313); Ultra-rare (popmax 0.028%, nfe).

How common is CEP97 p.Ser701Phe (c.2102C>T) in the general population?

CEP97 p.Ser701Phe (c.2102C>T) is ultra-rare (popmax 0.028%, nfe) (gnomAD).

What do computational predictors say about CEP97 p.Ser701Phe (c.2102C>T)?

AlphaMissense predicts likely pathogenic (score 0.7313) — an in-silico prediction, not a clinical call.

CEP97 p.Ser701Phe

c.2102C>T · rs368747293 · VCV2398119

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.7313 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.028%, nfe)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.7313	likely pathogenic
REVEL	0.333	indeterminate
SaProt	LLR -8.59	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 1.7, phastCons 1
Regional constraint	o/e 0.93	unconstrained · MANE · 41 kb · p 0.018 · regional, not allelic
Overall
CADD	27.0	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.028% European (non-Finnish) · 330/1,180,038 alleles

Filtering AF 0.0254% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0244%

Overall 0.0216% 348/1,614,010 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.028%	3,576
Remaining individualsnot grpmax-eligible	0.0224%	4,463
African / African-American	0.00534%	18,728

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.Ser701Phe
Coding: c.2102C>T
MANE Select: NM_024548
dbSNP: rs368747293
Type: single nucleotide variant
Location: chr3:101765055 (GRCh38)
Gene constraint: LOEUF 0.847 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 58.89
Residue 701: the 'ccp110-binding' region; the 'interaction with mphosph9' region

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

Similar variants

CEP97 p.Ser701Cys Uncertain significance ★ ⚠ same residue
CEP97 p.Ala164Thr Uncertain significance ★★ ⚠ same type
CEP97 p.Ala624Gly Uncertain significance ★★ ⚠ same type
CEP97 p.Arg259Gln Uncertain significance ★★ ⚠ same type
CEP97 p.Arg468Ile Uncertain significance ★★ ⚠ same type
CEP97 p.Arg570Gln Uncertain significance ★★ ⚠ same type
CEP97 p.Arg585Cys Uncertain significance ★★ ⚠ same type
CEP97 p.Arg591Cys Uncertain significance ★★ ⚠ 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-ser701phe (accessed [today's date]).

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