Is CPLANE1 p.Ser1127Ter (c.3380C>A) pathogenic?

CPLANE1 p.Ser1127Ter (c.3380C>A) is classified Pathogenic in CPLANE1 (ClinVar, Single submitter, 1 submitter; last evaluated 2015-04-23). Very rare (popmax 8.47e-05%, nfe).

How common is CPLANE1 p.Ser1127Ter (c.3380C>A) in the general population?

CPLANE1 p.Ser1127Ter (c.3380C>A) is very rare (popmax 8.47e-05%, nfe) (gnomAD).

CPLANE1 p.Ser1127Ter

c.3380C>A · rs375009168 · VCV279720

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 8.47e-05%, nfe)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function
NMD	predicted	premature termination codon in exon 19 of 53
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 1.7, phastCons 1
Overall
CADD	37.0	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.47e-05% European (non-Finnish) · 1/1,179,954 alleles

Overall 6.84e-05% 1/1,461,772 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.Ser1127Ter
Coding: c.3380C>A
MANE Select: NM_001384732
dbSNP: rs375009168
Type: single nucleotide variant
Location: chr5:37201718 (GRCh38)
Gene constraint: LOEUF 0.728 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Residue 1127: a UniProt-annotated variant site (in ofd6)

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

Similar variants

CPLANE1 p.Ser1127Leu Pathogenic/Likely pathogenic ★★ ⚠ same residue
CPLANE1 p.Ser1127Ala Uncertain significance ★★ ⚠ same residue
CPLANE1 p.Ser1127= Likely benign ★★ same residue
CPLANE1 c.1372-2A>G Pathogenic/Likely pathogenic ★★ same type
CPLANE1 c.2291+1G>A Likely pathogenic ★★ same type
CPLANE1 c.2291+2T>C Pathogenic/Likely pathogenic ★★ same type
CPLANE1 c.2292-1G>A Likely pathogenic ★★ same type
CPLANE1 c.2500+1G>A Likely pathogenic ★★ 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/cplane1-p-ser1127ter (accessed [today's date]).

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