Is CPLANE1 p.Phe1580Ser (c.4739T>C) pathogenic?

CPLANE1 p.Phe1580Ser (c.4739T>C) is classified Uncertain significance in CPLANE1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2023-05-15). AlphaMissense: likely pathogenic (0.716); Very rare (popmax 0.004%, afr).

How common is CPLANE1 p.Phe1580Ser (c.4739T>C) in the general population?

CPLANE1 p.Phe1580Ser (c.4739T>C) is very rare (popmax 0.004%, afr) (gnomAD).

What do computational predictors say about CPLANE1 p.Phe1580Ser (c.4739T>C)?

AlphaMissense predicts likely pathogenic (score 0.716) — an in-silico prediction, not a clinical call.

CPLANE1 p.Phe1580Ser

c.4739T>C · rs1027538017 · VCV1334822

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.716 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.004%, afr)

Computational evidence

Protein change
AlphaMissense	0.716	likely pathogenic · top 8% in CPLANE1
REVEL	0.538	indeterminate
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.3	GERP 1.6, phastCons 1
Regional constraint	o/e 0.92	unconstrained · MANE · 139 kb · p 2.3e-06 · regional, not allelic
Overall
CADD	24.4	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 0.004% African / African-American · 3/74,920 alleles

Filtering AF 0.00106% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000495%

Overall 0.000248% 4/1,613,646 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.004%	24,973
South Asian	0.0011%	91,070

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.Phe1580Ser
Coding: c.4739T>C
MANE Select: NM_001384732
dbSNP: rs1027538017
Type: single nucleotide variant
Location: chr5:37183442 (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 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
CPLANE1 c.3673-1G>C 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-phe1580ser (accessed [today's date]).

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