Is CPLANE1 p.Phe2033Cys (c.6098T>G) pathogenic?

CPLANE1 p.Phe2033Cys (c.6098T>G) is classified Benign/Likely benign in CPLANE1 (ClinVar, Multiple submitters, 11 submitters; last evaluated 2026-03-30). AlphaMissense: likely benign (0.0434); Common (popmax 31.2%, afr) — too common for a highly-penetrant pathogenic allele; Associated with Joubert syndrome 17.

What condition is associated with CPLANE1 p.Phe2033Cys (c.6098T>G)?

CPLANE1 p.Phe2033Cys (c.6098T>G) is associated with Joubert syndrome 17 (ClinVar).

What do computational predictors say about CPLANE1 p.Phe2033Cys (c.6098T>G)?

AlphaMissense predicts likely benign (score 0.0434) — an in-silico prediction, not a clinical call.

CPLANE1 p.Phe2033Cys

Q: How common is CPLANE1 p.Phe2033Cys (c.6098T>G) in the general population?

CPLANE1 p.Phe2033Cys (c.6098T>G) is common (popmax 31.2%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.6098T>G · rs10076911 · VCV158048

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 11 submitters

AlphaMissense

likely benign

0.0434 · ACMG-weighted

gnomAD v4.1

Common

common (popmax 31.2%, afr) — too common for a highly-penetrant pathogenic allele

Missense predictors

0/2 damaging

AlphaMissense, REVEL

Conditions

Joubert syndrome 17

Computational evidence

Protein change
AlphaMissense	0.0434	likely benign
REVEL	0.046	moderately benign-leaning
⇒ AlphaMissense and REVEL both call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.6	GERP -2.8, phastCons 0.025
Regional constraint	o/e 0.92	unconstrained · MANE · 139 kb · p 2.3e-06 · regional, not allelic
Overall
CADD	6.023	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 31.2% African / African-American · 23,405/74,914 alleles

Filtering AF 30.9% ClinGen BA1/BS1 input FAF95, joint · FAF99 30.8%

Overall 11.6% 187,365/1,613,758 alleles · common

Ancestry group	Frequency	1 in
African / African-Americangrpmax	31.2%	3
Admixed American	18.1%	6
Ashkenazi Jewishnot grpmax-eligible	16.2%	6
Middle Eastern	13.7%	7
Finnishnot grpmax-eligible	13%	8
Remaining individualsnot grpmax-eligible	12.6%	8
South Asian	10.3%	10
European (non-Finnish)	10.1%	10
East Asian	5.96%	17
Amishnot grpmax-eligible	3.51%	29

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: CPLANE1
Protein: p.Phe2033Cys
Coding: c.6098T>G
MANE Select: NM_001384732
dbSNP: rs10076911
Type: single nucleotide variant
Location: chr5:37173828 (GRCh38)
Gene constraint: LOEUF 0.728 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Residue 2033: a UniProt-annotated variant site (in)

Full CPLANE1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Joubert syndrome 17 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CPLANE1 p.Phe2033_Thr2034delinsCysMet Uncertain significance ★ same residue
CPLANE1 c.1372-2A>G Pathogenic/Likely pathogenic ★★ same condition
CPLANE1 c.2291+1G>A Likely pathogenic ★★ same condition
CPLANE1 c.2291+2T>C Pathogenic/Likely pathogenic ★★ same condition
CPLANE1 c.2292-1G>A Likely pathogenic ★★ same condition
CPLANE1 c.2500+1G>A Likely pathogenic ★★ same condition
CPLANE1 c.3290-2A>G Pathogenic/Likely pathogenic ★★ same condition
CPLANE1 c.3673-1G>C Pathogenic/Likely pathogenic ★★ same condition

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/cplane1-p-phe2033cys (accessed [today's date]).

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