Is CLSTN3 p.Pro96Ala (c.286C>G) pathogenic?

CLSTN3 p.Pro96Ala (c.286C>G) is classified Uncertain significance in CLSTN3 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-20). AlphaMissense: likely benign (0.0636); Very rare (popmax 0.00373%, nfe).

How common is CLSTN3 p.Pro96Ala (c.286C>G) in the general population?

CLSTN3 p.Pro96Ala (c.286C>G) is very rare (popmax 0.00373%, nfe) (gnomAD).

What do computational predictors say about CLSTN3 p.Pro96Ala (c.286C>G)?

AlphaMissense predicts likely benign (score 0.0636) — an in-silico prediction, not a clinical call.

CLSTN3 p.Pro96Ala

c.286C>G · rs150647098 · VCV3146082

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0636 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00373%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0636	likely benign
REVEL	0.175	moderately benign-leaning
SaProt	LLR -7.25	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.8	GERP -1.1, phastCons 1
Regional constraint	o/e 0.85	unconstrained · MANE · 27 kb · p 2.1e-07 · regional, not allelic
Overall
CADD	27.5	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 and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00373% European (non-Finnish) · 44/1,179,998 alleles

Filtering AF 0.00283% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00252%

Overall 0.00273% 44/1,613,962 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: CLSTN3
Protein: p.Pro96Ala
Coding: c.286C>G
MANE Select: NM_014718
dbSNP: rs150647098
Type: single nucleotide variant
Location: chr12:7133671 (GRCh38)
Gene constraint: LOEUF 0.508 · pLI 0.86 (gnomAD)
Structure: AlphaFold pLDDT 77.80
Residue 96: the cadherin 1 domain

Full CLSTN3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CLSTN3 p.Arg806Trp Uncertain significance ★★ ⚠ same type
CLSTN3 p.Ala11Val Uncertain significance ★ ⚠ same type
CLSTN3 p.Ala152Val Uncertain significance ★ ⚠ same type
CLSTN3 p.Ala153Thr Uncertain significance ★ ⚠ same type
CLSTN3 p.Ala304Val Uncertain significance ★ ⚠ same type
CLSTN3 p.Ala312Pro Uncertain significance ★ ⚠ same type
CLSTN3 p.Ala312Val Uncertain significance ★ ⚠ same type
CLSTN3 p.Ala451Thr Uncertain significance ★ ⚠ 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/clstn3-p-pro96ala (accessed [today's date]).

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