Is CEP295 p.Ala488Val (c.1463C>T) pathogenic?

CEP295 p.Ala488Val (c.1463C>T) is classified Uncertain significance in CEP295 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-08-12). AlphaMissense: likely benign (0.1469); Ultra-rare (popmax 0.0275%, amr).

How common is CEP295 p.Ala488Val (c.1463C>T) in the general population?

CEP295 p.Ala488Val (c.1463C>T) is ultra-rare (popmax 0.0275%, amr) (gnomAD).

What do computational predictors say about CEP295 p.Ala488Val (c.1463C>T)?

AlphaMissense predicts likely benign (score 0.1469) — an in-silico prediction, not a clinical call.

CEP295 p.Ala488Val

c.1463C>T · rs184603353 · VCV2244343

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1469 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0275%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1469	likely benign
REVEL	0.025	moderately benign-leaning
SaProt	LLR -6.24	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>G here scores Δ0.57 · evaluated, not missing
Constraint at this position
Conservation	phyloP 1.1	GERP 1, phastCons 0.59
Regional constraint	o/e 0.96	unconstrained · MANE · 25 kb · p 0.36 · regional, not allelic
Overall
CADD	19.57	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0275% Admixed American · 14/50,868 alleles

Filtering AF 0.0166% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0133%

Overall 0.000906% 14/1,545,962 alleles · ultra-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: CEP295
Protein: p.Ala488Val
Coding: c.1463C>T
MANE Select: NM_033395
dbSNP: rs184603353
Type: single nucleotide variant
Location: chr11:93691960 (GRCh38)
Gene constraint: LOEUF 0.735 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 44.76
Residue 488: 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-ala488val (accessed [today's date]).

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