Is CEP295 p.Ile2052Val (c.6154A>G) pathogenic?

CEP295 p.Ile2052Val (c.6154A>G) is classified Uncertain significance in CEP295 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-12-16). AlphaMissense: likely benign (0.1034); Rare (popmax 0.108%, nfe).

How common is CEP295 p.Ile2052Val (c.6154A>G) in the general population?

CEP295 p.Ile2052Val (c.6154A>G) is rare (popmax 0.108%, nfe) (gnomAD).

What do computational predictors say about CEP295 p.Ile2052Val (c.6154A>G)?

AlphaMissense predicts likely benign (score 0.1034) — an in-silico prediction, not a clinical call.

CEP295 p.Ile2052Val

c.6154A>G · rs200980804 · VCV3142843

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1034 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.108%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1034	likely benign
REVEL	0.016	strongly benign-leaning
SaProt	LLR -6.16	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	Δ0.22	donor gain · deltas
Constraint at this position
Conservation	phyloP 2.1	GERP 1.7, phastCons 0.001
Regional constraint	o/e 0.98	unconstrained · MANE · 35 kb · p 0.4 · regional, not allelic
Overall
CADD	18.73	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 0.108% European (non-Finnish) · 1,237/1,141,584 alleles

Filtering AF 0.103% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.101%

Overall 0.0896% 1,380/1,540,648 alleles · rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.108%	923
Remaining individualsnot grpmax-eligible	0.077%	1,299
Finnishnot grpmax-eligible	0.0534%	1,871
Admixed American	0.0427%	2,343
South Asian	0.0319%	3,134
African / African-American	0.022%	4,547
Ashkenazi Jewishnot grpmax-eligible	0.00706%	14,155

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.Ile2052Val
Coding: c.6154A>G
MANE Select: NM_033395
dbSNP: rs200980804
Type: single nucleotide variant
Location: chr11:93723247 (GRCh38)
Gene constraint: LOEUF 0.735 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 44.76
Residue 2052: 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-ile2052val (accessed [today's date]).

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