Is CPLANE1 p.Ala158= (c.474G>A) pathogenic?

CPLANE1 p.Ala158= (c.474G>A) is classified Uncertain significance in CPLANE1 (ClinVar, Multiple submitters, 5 submitters; last evaluated 2025-05-14). Very rare (popmax 0.00296%, nfe); Associated with autoimmune interstitial lung disease-arthritis syndrome.

What condition is associated with CPLANE1 p.Ala158= (c.474G>A)?

CPLANE1 p.Ala158= (c.474G>A) is associated with autoimmune interstitial lung disease-arthritis syndrome (ClinVar).

How common is CPLANE1 p.Ala158= (c.474G>A) in the general population?

CPLANE1 p.Ala158= (c.474G>A) is very rare (popmax 0.00296%, nfe) (gnomAD).

CPLANE1 p.Ala158=

Q: How is Autoimmune interstitial lung disease-arthritis syndrome inherited?

Typically Autosomal dominant (Orphanet). A genetic counselor can assess individual risk for a family.

c.474G>A · rs977870859 · VCV1297551

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00296%, nfe)

Conditions

autoimmune interstitial lung disease-arthritis syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Splicing
SpliceAI	Δ0.88	acceptor gain · deltas
Pangolin	Δ0.74	gain · loss 0.00 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 0.59	GERP 0.9, phastCons 0.1
Overall
CADD	13.41	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00296% European (non-Finnish) · 34/1,147,020 alleles

Filtering AF 0.00213% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00188%

Overall 0.00245% 38/1,551,714 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00296%	33,736
African / African-American	0.00274%	36,488
Remaining individualsnot grpmax-eligible	0.00166%	60,200
South Asian	0.00119%	84,046

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.Ala158=
Coding: c.474G>A
MANE Select: NM_001384732
dbSNP: rs977870859
Type: single nucleotide variant
Location: chr5:37244471 (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

Disease context

autoimmune interstitial lung disease-arthritis syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Autoimmune interstitial lung disease-arthritis syndrome (Orphanet):

Inheritance: Autosomal dominant
Onset: Childhood, Infancy

Similar variants

CPLANE1 p.Ala158Val 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-ala158 (accessed [today's date]).

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