Is CPLANE2 p.Arg34Trp (c.100C>T) pathogenic?

CPLANE2 p.Arg34Trp (c.100C>T) is classified Uncertain significance in CPLANE2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-07-14). AlphaMissense: ambiguous (0.4171); Very rare (popmax 0.00408%, afr).

How common is CPLANE2 p.Arg34Trp (c.100C>T) in the general population?

CPLANE2 p.Arg34Trp (c.100C>T) is very rare (popmax 0.00408%, afr) (gnomAD).

What do computational predictors say about CPLANE2 p.Arg34Trp (c.100C>T)?

AlphaMissense predicts ambiguous (score 0.4171) — an in-silico prediction, not a clinical call.

CPLANE2 p.Arg34Trp

c.100C>T · VCV4233345

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4171 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00408%, afr)

Missense predictors

2/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.4171	ambiguous
REVEL	0.746	pathogenic-leaning
SaProt	LLR -15.77	damaging
⇒ REVEL and SaProt both call this damaging; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.3	phastCons 1
Regional constraint	o/e 0.93	unconstrained · MANE · 4,691 bp · p 0.18 · regional, not allelic
Overall
CADD	31.0	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 0.00408% African / African-American · 3/73,482 alleles

Filtering AF 0.00108% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000501%

Overall 0.000514% 8/1,555,868 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00408%	24,494
Remaining individualsnot grpmax-eligible	0.00166%	60,218
European (non-Finnish)	0.000348%	287,204

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.Arg34Trp
Coding: c.100C>T
MANE Select: NM_030907
Type: single nucleotide variant
Location: chr1:16236643 (GRCh38)
Gene constraint: LOEUF 1.649 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 90.38

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

Similar variants

CPLANE2 p.Arg34Leu Uncertain significance ★ ⚠ same residue
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

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-arg34trp (accessed [today's date]).

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