Is CPLANE1 p.Met2927Val (c.8779A>G) pathogenic?

CPLANE1 p.Met2927Val (c.8779A>G) is classified Likely benign in CPLANE1 (ClinVar, Multiple submitters, 8 submitters; last evaluated 2026-02-01). AlphaMissense: likely benign (0.0794); Rare (popmax 0.582%, afr); Associated with Inborn genetic diseases.

What condition is associated with CPLANE1 p.Met2927Val (c.8779A>G)?

CPLANE1 p.Met2927Val (c.8779A>G) is associated with Inborn genetic diseases (ClinVar).

How common is CPLANE1 p.Met2927Val (c.8779A>G) in the general population?

CPLANE1 p.Met2927Val (c.8779A>G) is rare (popmax 0.582%, afr) (gnomAD).

What do computational predictors say about CPLANE1 p.Met2927Val (c.8779A>G)?

AlphaMissense predicts likely benign (score 0.0794) — an in-silico prediction, not a clinical call.

CPLANE1 p.Met2927Val

c.8779A>G · rs143626904 · VCV197531

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 8 submitters

AlphaMissense

likely benign

0.0794 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.582%, afr)

Missense predictors

0/2 damaging

AlphaMissense, REVEL

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0794	likely benign
REVEL	0.023	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 0.5	GERP -0.003
Regional constraint	o/e 0.92	unconstrained · MANE · 139 kb · p 2.3e-06 · regional, not allelic
Overall
CADD	12.57	PHRED · no single calibrated threshold — expert panels disagree

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

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM M2873V vs ClinVar M2927V) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.582% African / African-American · 436/74,920 alleles

Filtering AF 0.537% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.519%

Overall 0.0307% 495/1,610,410 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.582%	172
Remaining individualsnot grpmax-eligible	0.0417%	2,399
Admixed American	0.0406%	2,466
Middle Eastern	0.0166%	6,032
South Asian	0.00557%	17,956
European (non-Finnish)	0.000254%	392,994

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.Met2927Val
Coding: c.8779A>G
MANE Select: NM_001384732
dbSNP: rs143626904
Type: single nucleotide variant
Location: chr5:37138733 (GRCh38)
Gene constraint: LOEUF 0.728 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Residue 2927: 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-met2927val (accessed [today's date]).

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