Is CPLANE1 p.Lys491Arg (c.1472A>G) pathogenic?

CPLANE1 p.Lys491Arg (c.1472A>G) is classified Uncertain significance in CPLANE1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-10-20). AlphaMissense: likely benign (0.0604); Very rare (popmax 0.00489%, eas).

How common is CPLANE1 p.Lys491Arg (c.1472A>G) in the general population?

CPLANE1 p.Lys491Arg (c.1472A>G) is very rare (popmax 0.00489%, eas) (gnomAD).

What do computational predictors say about CPLANE1 p.Lys491Arg (c.1472A>G)?

AlphaMissense predicts likely benign (score 0.0604) — an in-silico prediction, not a clinical call.

CPLANE1 p.Lys491Arg

c.1472A>G · rs761746624 · VCV2139281

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0604 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00489%, eas)

Missense predictors

0/2 damaging

AlphaMissense, REVEL

Computational evidence

Protein change
AlphaMissense	0.0604	likely benign
REVEL	0.014	strongly benign-leaning
⇒ AlphaMissense and REVEL both call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.23	GERP -2.9
Regional constraint	o/e 0.92	unconstrained · MANE · 139 kb · p 2.3e-06 · regional, not allelic
Overall
CADD	2.989	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00489% East Asian · 2/40,880 alleles

Filtering AF 0.000811% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000303%

Overall 0.000451% 7/1,552,206 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00489%	20,440
Remaining individualsnot grpmax-eligible	0.00332%	30,146
South Asian	0.00238%	42,025
African / African-American	0.00137%	73,170

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.Lys491Arg
Coding: c.1472A>G
MANE Select: NM_001384732
dbSNP: rs761746624
Type: single nucleotide variant
Location: chr5:37227292 (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

Similar variants

CPLANE1 p.Lys491Ile Uncertain significance ★★ ⚠ 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
CPLANE1 c.2920+1G>A Likely pathogenic ★★ same type
CPLANE1 c.3290-2A>G Pathogenic/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-lys491arg (accessed [today's date]).

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