Is CEP295 p.Leu1732Pro (c.5195T>C) pathogenic?

CEP295 p.Leu1732Pro (c.5195T>C) is classified Uncertain significance in CEP295 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-12-11). AlphaMissense: likely benign (0.2825); Rare (popmax 0.225%, eas).

How common is CEP295 p.Leu1732Pro (c.5195T>C) in the general population?

CEP295 p.Leu1732Pro (c.5195T>C) is rare (popmax 0.225%, eas) (gnomAD).

What do computational predictors say about CEP295 p.Leu1732Pro (c.5195T>C)?

AlphaMissense predicts likely benign (score 0.2825) — an in-silico prediction, not a clinical call.

CEP295 p.Leu1732Pro

c.5195T>C · rs192763656 · VCV2375113

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2825 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.225%, eas)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.2825	likely benign
REVEL	0.319	indeterminate
SaProt	LLR -14.01	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.26	GERP -3.8, phastCons 0.054
Regional constraint	o/e 0.98	unconstrained · MANE · 35 kb · p 0.4 · regional, not allelic
Overall
CADD	15.85	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 0.225% East Asian · 92/40,904 alleles

Filtering AF 0.188% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.174%

Overall 0.0124% 193/1,551,746 alleles · rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.225%	445
South Asian	0.0547%	1,828
Remaining individualsnot grpmax-eligible	0.00998%	10,025
African / African-American	0.0041%	24,390
European (non-Finnish)	0.00401%	24,934

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.Leu1732Pro
Coding: c.5195T>C
MANE Select: NM_033395
dbSNP: rs192763656
Type: single nucleotide variant
Location: chr11:93700107 (GRCh38)
Gene constraint: LOEUF 0.735 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 44.76
Residue 1732: 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-leu1732pro (accessed [today's date]).

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