Is CPLANE1 p.Thr379Met (c.1136C>T) pathogenic?

CPLANE1 p.Thr379Met (c.1136C>T) is classified Benign/Likely benign in CPLANE1 (ClinVar, Multiple submitters, 5 submitters; last evaluated 2026-02-02). AlphaMissense: likely benign (0.077); Low-frequency (popmax 1.08%, sas); Associated with Joubert syndrome 17.

What condition is associated with CPLANE1 p.Thr379Met (c.1136C>T)?

CPLANE1 p.Thr379Met (c.1136C>T) is associated with Joubert syndrome 17 (ClinVar).

How common is CPLANE1 p.Thr379Met (c.1136C>T) in the general population?

CPLANE1 p.Thr379Met (c.1136C>T) is low-frequency (popmax 1.08%, sas) (gnomAD).

What do computational predictors say about CPLANE1 p.Thr379Met (c.1136C>T)?

AlphaMissense predicts likely benign (score 0.077) — an in-silico prediction, not a clinical call.

CPLANE1 p.Thr379Met

c.1136C>T · rs373606997 · VCV714360

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

AlphaMissense

likely benign

0.077 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 1.08%, sas)

Missense predictors

0/2 damaging

AlphaMissense, REVEL

Conditions

Joubert syndrome 17

Computational evidence

Protein change
AlphaMissense	0.077	likely benign
REVEL	0.027	moderately benign-leaning
⇒ AlphaMissense and REVEL both call this tolerated.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>C here scores Δ0.26 · evaluated, not missing
Constraint at this position
Conservation	phyloP 2.7	GERP -1.2, phastCons 0.67
Regional constraint	o/e 0.92	unconstrained · MANE · 139 kb · p 2.3e-06 · regional, not allelic
Overall
CADD	15.31	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 1.08% South Asian · 904/83,936 alleles

Filtering AF 1.02% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.995%

Overall 0.0622% 964/1,550,344 alleles · low-frequency

Ancestry group	Frequency	1 in
South Asiangrpmax	1.08%	93
Remaining individualsnot grpmax-eligible	0.0749%	1,335
Middle Eastern	0.0669%	1,494
African / African-American	0.00274%	36,561
European (non-Finnish)	0.000785%	127,378

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.Thr379Met
Coding: c.1136C>T
MANE Select: NM_001384732
dbSNP: rs373606997
Type: single nucleotide variant
Location: chr5:37227803 (GRCh38)
Gene constraint: LOEUF 0.728 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)

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.Thr379= Likely benign ★ 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-thr379met (accessed [today's date]).

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