Is CLSTN3 p.Thr511= (c.1533C>T) pathogenic?

CLSTN3 p.Thr511= (c.1533C>T) is classified Likely benign in CLSTN3 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-03-01). Very rare (popmax 0.000255%, nfe).

How common is CLSTN3 p.Thr511= (c.1533C>T) in the general population?

CLSTN3 p.Thr511= (c.1533C>T) is very rare (popmax 0.000255%, nfe) (gnomAD).

CLSTN3 p.Thr511=

c.1533C>T · rs1393797216 · VCV2642666

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.000255%, nfe)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.4	GERP -2.3
Overall
CADD	6.383	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000255% European (non-Finnish) · 3/1,176,532 alleles

Filtering AF 6.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.9e-05%

Overall 0.000206% 3/1,457,292 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.Thr511=
Coding: c.1533C>T
MANE Select: NM_014718
dbSNP: rs1393797216
Type: single nucleotide variant
Location: chr12:7142132 (GRCh38)
Gene constraint: LOEUF 0.508 · pLI 0.86 (gnomAD)
Structure: AlphaFold pLDDT 77.80

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-thr511 (accessed [today's date]).

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