Is CPLANE1 p.Val1114Glu (c.3341T>A) pathogenic?

CPLANE1 p.Val1114Glu (c.3341T>A) is classified Uncertain significance in CPLANE1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2021-06-06). AlphaMissense: likely pathogenic (0.7589); Very rare (popmax 0.000847%, nfe); Associated with Inborn genetic diseases.

What condition is associated with CPLANE1 p.Val1114Glu (c.3341T>A)?

CPLANE1 p.Val1114Glu (c.3341T>A) is associated with Inborn genetic diseases (ClinVar).

How common is CPLANE1 p.Val1114Glu (c.3341T>A) in the general population?

CPLANE1 p.Val1114Glu (c.3341T>A) is very rare (popmax 0.000847%, nfe) (gnomAD).

What do computational predictors say about CPLANE1 p.Val1114Glu (c.3341T>A)?

AlphaMissense predicts likely pathogenic (score 0.7589) — an in-silico prediction, not a clinical call.

CPLANE1 p.Val1114Glu

c.3341T>A · rs746467519 · VCV288020

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.7589 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000847%, nfe)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.7589	likely pathogenic · top 7% in CPLANE1
REVEL	0.553	indeterminate
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.4	GERP 1.7, phastCons 1
Regional constraint	o/e 0.92	unconstrained · MANE · 139 kb · p 2.3e-06 · regional, not allelic
Overall
CADD	24.7	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 0.000847% European (non-Finnish) · 10/1,179,964 alleles

Filtering AF 0.000429% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000312%

Overall 0.000684% 10/1,461,734 alleles · very rare

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.Val1114Glu
Coding: c.3341T>A
MANE Select: NM_001384732
dbSNP: rs746467519
Type: single nucleotide variant
Location: chr5:37201757 (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

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CPLANE1 p.Val1114Leu Uncertain significance ★ same residue
CPLANE1 c.3921+6T>G Uncertain significance ★★ same condition
CPLANE1 p.Ala77Ser Uncertain significance ★★ ⚠ same condition
CPLANE1 p.Arg1199Gln Uncertain significance ★★ ⚠ same condition
CPLANE1 p.Arg3015Cys Uncertain significance ★★ ⚠ same condition
CPLANE1 p.Asp2526Asn Uncertain significance ★★ ⚠ same condition
CPLANE1 p.Cys1280Tyr Uncertain significance ★★ ⚠ same condition
CPLANE1 p.Cys3057Gly Uncertain significance ★★ ⚠ 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-val1114glu (accessed [today's date]).

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