Is CPLANE2 p.Val94Met (c.280G>A) pathogenic?

CPLANE2 p.Val94Met (c.280G>A) is classified Uncertain significance in CPLANE2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-04-20). AlphaMissense: likely benign (0.1502); Ultra-rare (popmax 0.0307%, afr).

How common is CPLANE2 p.Val94Met (c.280G>A) in the general population?

CPLANE2 p.Val94Met (c.280G>A) is ultra-rare (popmax 0.0307%, afr) (gnomAD).

What do computational predictors say about CPLANE2 p.Val94Met (c.280G>A)?

AlphaMissense predicts likely benign (score 0.1502) — an in-silico prediction, not a clinical call.

CPLANE2 p.Val94Met

c.280G>A · VCV3269184

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1502 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0307%, afr)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1502	likely benign
REVEL	0.081	moderately benign-leaning
SaProt	LLR -10.17	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.3	phastCons 1
Regional constraint	o/e 0.93	unconstrained · MANE · 4,691 bp · p 0.18 · regional, not allelic
Overall
CADD	24.2	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 0.0307% African / African-American · 23/74,912 alleles

Filtering AF 0.021% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0178%

Overall 0.00397% 64/1,613,972 alleles · ultra-rare exomes 55/1,461,836 · genomes 9/152,136 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0307%	3,257
Admixed American	0.0217%	4,614
Remaining individualsnot grpmax-eligible	0.0144%	6,943
South Asian	0.00769%	13,012
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,604
East Asian	0.00223%	44,890
European (non-Finnish)	0.000847%	118,002

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.Val94Met
Coding: c.280G>A
MANE Select: NM_030907
Type: single nucleotide variant
Location: chr1:16233003 (GRCh38)
Gene constraint: LOEUF 1.649 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 90.38
Residue 94: 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-val94met (accessed [today's date]).

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