Is CPLANE2 p.Thr88= (c.264C>T) pathogenic?

CPLANE2 p.Thr88= (c.264C>T) is classified Likely benign in CPLANE2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-12-06). Rare (popmax 0.141%, afr).

How common is CPLANE2 p.Thr88= (c.264C>T) in the general population?

CPLANE2 p.Thr88= (c.264C>T) is rare (popmax 0.141%, afr) (gnomAD).

CPLANE2 p.Thr88=

c.264C>T · VCV3496408

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

rare (popmax 0.141%, afr)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.028	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -5.7
Overall
CADD	0.132	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.141% African / African-American · 106/75,058 alleles

Filtering AF 0.119% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.111%

Overall 0.00967% 156/1,614,014 alleles · rare exomes 94/1,461,666 · genomes 62/152,348 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.141%	708
Remaining individualsnot grpmax-eligible	0.0096%	10,418
Admixed American	0.00666%	15,005
East Asian	0.00446%	22,441
South Asian	0.00329%	30,357
European (non-Finnish)	0.00297%	33,714

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: CPLANE2
Protein: p.Thr88=
Coding: c.264C>T
MANE Select: NM_030907
Type: single nucleotide variant
Location: chr1:16233613 (GRCh38)
Gene constraint: LOEUF 1.649 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 90.38
Residue 88: the 'small gtpase-like' region

Full CPLANE2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CPLANE2 p.Arg106Cys Uncertain significance ★ ⚠ same type
CPLANE2 p.Arg106His Uncertain significance ★ ⚠ same type
CPLANE2 p.Arg111Cys Uncertain significance ★ ⚠ same type
CPLANE2 p.Arg148Cys Uncertain significance ★ ⚠ same type
CPLANE2 p.Arg160Cys Uncertain significance ★ ⚠ same type
CPLANE2 p.Arg160His Uncertain significance ★ ⚠ same type
CPLANE2 p.Arg188Gln Uncertain significance ★ ⚠ same type
CPLANE2 p.Arg188Trp Uncertain significance ★ ⚠ 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/cplane2-p-thr88 (accessed [today's date]).

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