Is CPLANE1 p.Ala77Ser (c.229G>T) pathogenic?

CPLANE1 p.Ala77Ser (c.229G>T) is classified Uncertain significance in CPLANE1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-03-01). AlphaMissense: likely benign (0.1531); Very rare (popmax 0.00115%, nfe); Associated with Inborn genetic diseases.

What condition is associated with CPLANE1 p.Ala77Ser (c.229G>T)?

CPLANE1 p.Ala77Ser (c.229G>T) is associated with Inborn genetic diseases (ClinVar).

How common is CPLANE1 p.Ala77Ser (c.229G>T) in the general population?

CPLANE1 p.Ala77Ser (c.229G>T) is very rare (popmax 0.00115%, nfe) (gnomAD).

What do computational predictors say about CPLANE1 p.Ala77Ser (c.229G>T)?

AlphaMissense predicts likely benign (score 0.1531) — an in-silico prediction, not a clinical call.

CPLANE1 p.Ala77Ser

c.229G>T · rs1441701659 · VCV3076679

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1531 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00115%, nfe)

Missense predictors

0/2 damaging

AlphaMissense, REVEL · SaProt no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1531	likely benign
REVEL	0.049	moderately benign-leaning
SaProt	—	not scored · why
⇒ AlphaMissense and REVEL both call this tolerated; SaProt makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.4	GERP 0.82, phastCons 1
Regional constraint	o/e 0.92	unconstrained · MANE · 139 kb · p 2.3e-06 · regional, not allelic
Overall
CADD	19.7	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 is an independent agreement signal.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00115% European (non-Finnish) · 13/1,132,318 alleles

Filtering AF 0.000641% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000494%

Overall 0.000858% 13/1,515,408 alleles · very rare

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.Ala77Ser
Coding: c.229G>T
MANE Select: NM_001384732
dbSNP: rs1441701659
Type: single nucleotide variant
Location: chr5:37245587 (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

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.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
CPLANE1 p.Gln1295Pro 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-ala77ser (accessed [today's date]).

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