Is CEP295 p.Gln712Pro (c.2135A>C) pathogenic?

CEP295 p.Gln712Pro (c.2135A>C) is classified Uncertain significance in CEP295 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-25). AlphaMissense: likely benign (0.0982); Ultra-rare (popmax 0.0195%, eas).

How common is CEP295 p.Gln712Pro (c.2135A>C) in the general population?

CEP295 p.Gln712Pro (c.2135A>C) is ultra-rare (popmax 0.0195%, eas) (gnomAD).

What do computational predictors say about CEP295 p.Gln712Pro (c.2135A>C)?

AlphaMissense predicts likely benign (score 0.0982) — an in-silico prediction, not a clinical call.

CEP295 p.Gln712Pro

c.2135A>C · rs1412015699 · VCV2539091

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0982 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0195%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0982	likely benign
REVEL	0.113	moderately benign-leaning
SaProt	LLR -5.72	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 2.1	GERP -3, phastCons 0.29
Regional constraint	o/e 0.98	unconstrained · MANE · 35 kb · p 0.4 · regional, not allelic
Overall
CADD	15.68	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 0.0195% East Asian · 8/40,928 alleles

Filtering AF 0.00967% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00704%

Overall 0.000645% 10/1,551,504 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0195%	5,116
Remaining individualsnot grpmax-eligible	0.00166%	60,098
European (non-Finnish)	8.72e-05%	1,147,003

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.Gln712Pro
Coding: c.2135A>C
MANE Select: NM_033395
dbSNP: rs1412015699
Type: single nucleotide variant
Location: chr11:93697047 (GRCh38)
Gene constraint: LOEUF 0.735 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 44.76
Residue 712: 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-gln712pro (accessed [today's date]).

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