Is CPLANE1 p.Val2527Ile (c.7579G>A) pathogenic?

CPLANE1 p.Val2527Ile (c.7579G>A) is classified Conflicting classifications of pathogenicity in CPLANE1 (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2021-11-28). AlphaMissense: likely benign (0.0513); Very rare (popmax 0.00267%, afr); Associated with Inborn genetic diseases.

What condition is associated with CPLANE1 p.Val2527Ile (c.7579G>A)?

CPLANE1 p.Val2527Ile (c.7579G>A) is associated with Inborn genetic diseases (ClinVar).

How common is CPLANE1 p.Val2527Ile (c.7579G>A) in the general population?

CPLANE1 p.Val2527Ile (c.7579G>A) is very rare (popmax 0.00267%, afr) (gnomAD).

What do computational predictors say about CPLANE1 p.Val2527Ile (c.7579G>A)?

AlphaMissense predicts likely benign (score 0.0513) — an in-silico prediction, not a clinical call.

CPLANE1 p.Val2527Ile

c.7579G>A · rs749261159 · VCV1311394

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.0513 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00267%, afr)

Missense predictors

0/2 damaging

AlphaMissense, REVEL

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0513	likely benign
REVEL	0.032	moderately 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 0.89	GERP 0.24, phastCons 0.75
Regional constraint	o/e 0.92	unconstrained · MANE · 139 kb · p 2.3e-06 · regional, not allelic
Overall
CADD	12.78	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 0.00267% African / African-American · 2/74,792 alleles

Filtering AF 0.00069% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000539%

Overall 0.00118% 19/1,611,746 alleles · very rare

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0032%	31,203
African / African-Americangrpmax	0.00267%	37,396
European (non-Finnish)	0.00119%	84,154
South Asian	0.0011%	91,032

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Val2527Ile
Coding: c.7579G>A
MANE Select: NM_001384732
dbSNP: rs749261159
Type: single nucleotide variant
Location: chr5:37164282 (GRCh38)
Gene constraint: LOEUF 0.728 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Residue 2527: a UniProt-annotated variant site (in ofd6; likely pathogenic)

Full CPLANE1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CPLANE1 c.3921+6T>G Uncertain significance ★★ same condition
CPLANE1 p.Ala77Ser Uncertain significance ★★ ⚠ same condition
CPLANE1 p.Arg1199Gln Uncertain significance ★★ ⚠ same condition
CPLANE1 p.Arg3015Cys Uncertain significance ★★ ⚠ same condition
CPLANE1 p.Asp2526Asn Uncertain significance ★★ ⚠ same condition
CPLANE1 p.Cys1280Tyr Uncertain significance ★★ ⚠ same condition
CPLANE1 p.Cys3057Gly Uncertain significance ★★ ⚠ same condition
CPLANE1 p.Cys525Arg Uncertain significance ★★ ⚠ same condition

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-val2527ile (accessed [today's date]).

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