Is CEP295 p.Phe888Ser (c.2663T>C) pathogenic?

CEP295 p.Phe888Ser (c.2663T>C) is classified Benign in CEP295 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2017-08-02). AlphaMissense: likely benign (0.1395); Low-frequency (popmax 3.2%, afr).

How common is CEP295 p.Phe888Ser (c.2663T>C) in the general population?

CEP295 p.Phe888Ser (c.2663T>C) is low-frequency (popmax 3.2%, afr) (gnomAD).

What do computational predictors say about CEP295 p.Phe888Ser (c.2663T>C)?

AlphaMissense predicts likely benign (score 0.1395) — an in-silico prediction, not a clinical call.

CEP295 p.Phe888Ser

c.2663T>C · rs115822333 · VCV710064

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1395 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 3.2%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1395	likely benign
REVEL	0.013	strongly benign-leaning
SaProt	LLR -3.22	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.45	GERP -3
Regional constraint	o/e 0.98	unconstrained · MANE · 35 kb · p 0.4 · regional, not allelic
Overall
CADD	10.59	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 3.2% African / African-American · 2,341/73,160 alleles

Filtering AF 3.09% ClinGen BA1/BS1 input FAF95, joint · FAF99 3.05%

Overall 0.179% 2,772/1,551,750 alleles · low-frequency

Ancestry group	Frequency	1 in
African / African-Americangrpmax	3.2%	31
Admixed American	0.388%	258
Remaining individualsnot grpmax-eligible	0.261%	383
Middle Eastern	0.0834%	1,198
East Asian	0.022%	4,547
European (non-Finnish)	0.00506%	19,775
South Asian	0.00476%	21,016

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: CEP295
Protein: p.Phe888Ser
Coding: c.2663T>C
MANE Select: NM_033395
dbSNP: rs115822333
Type: single nucleotide variant
Location: chr11:93697575 (GRCh38)
Gene constraint: LOEUF 0.735 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 44.76
Residue 888: a UniProt-annotated variant site (in sckl11; likely pathogenic)

Full CEP295 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CEP295 p.Gln2146His Uncertain significance ★★ ⚠ same type
CEP295 p.Gln998Arg Uncertain significance ★★ ⚠ same type
CEP295 p.Thr451Arg Uncertain significance ★★ ⚠ same type
CEP295 p.Gln1506= Benign ★★ same type
CEP295 p.Gln1728= Benign ★★ same type
CEP295 p.Gln80Lys Benign ★★ same type
CEP295 p.Glu1026Lys Benign ★★ ⚠ same type
CEP295 p.Glu179Lys 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/cep295-p-phe888ser (accessed [today's date]).

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