Is CEP295 p.Ser440Phe (c.1319C>T) pathogenic?

CEP295 p.Ser440Phe (c.1319C>T) is classified Benign in CEP295 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2017-08-02). AlphaMissense: likely benign (0.1308); Low-frequency (popmax 3.24%, afr).

How common is CEP295 p.Ser440Phe (c.1319C>T) in the general population?

CEP295 p.Ser440Phe (c.1319C>T) is low-frequency (popmax 3.24%, afr) (gnomAD).

What do computational predictors say about CEP295 p.Ser440Phe (c.1319C>T)?

AlphaMissense predicts likely benign (score 0.1308) — an in-silico prediction, not a clinical call.

CEP295 p.Ser440Phe

c.1319C>T · rs60226346 · VCV710061

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1308 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 3.24%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1308	likely benign
REVEL	0.039	moderately benign-leaning
SaProt	LLR -7.56	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 1	GERP 0.59, phastCons 0.013
Regional constraint	o/e 0.96	unconstrained · MANE · 25 kb · p 0.36 · regional, not allelic
Overall
CADD	19.54	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 3.24% African / African-American · 2,367/73,086 alleles

Filtering AF 3.13% ClinGen BA1/BS1 input FAF95, joint · FAF99 3.09%

Overall 0.18% 2,797/1,550,136 alleles · low-frequency

Ancestry group	Frequency	1 in
African / African-Americangrpmax	3.24%	31
Admixed American	0.389%	257
Remaining individualsnot grpmax-eligible	0.26%	385
Middle Eastern	0.0835%	1,197
East Asian	0.022%	4,541
European (non-Finnish)	0.00506%	19,760
South Asian	0.00477%	20,950

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.Ser440Phe
Coding: c.1319C>T
MANE Select: NM_033395
dbSNP: rs60226346
Type: single nucleotide variant
Location: chr11:93687848 (GRCh38)
Gene constraint: LOEUF 0.735 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 44.76
Residue 440: the 'necessary for centriole targeting and microtubule association' region

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-ser440phe (accessed [today's date]).

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