Is CLASP2 p.Ile447= (c.1341A>T) pathogenic?

CLASP2 p.Ile447= (c.1341A>T) is classified Likely benign in CLASP2 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-07-23). Rare (popmax 0.154%, nfe); Associated with CLASP2-related disorder.

What condition is associated with CLASP2 p.Ile447= (c.1341A>T)?

CLASP2 p.Ile447= (c.1341A>T) is associated with CLASP2-related disorder (ClinVar).

How common is CLASP2 p.Ile447= (c.1341A>T) in the general population?

CLASP2 p.Ile447= (c.1341A>T) is rare (popmax 0.154%, nfe) (gnomAD).

CLASP2 p.Ile447=

c.1341A>T · rs142035502 · VCV3050689

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

rare (popmax 0.154%, nfe)

Conditions

CLASP2-related disorder

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 0.82	GERP -2.1, phastCons 1
Overall
CADD	5.481	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.154% European (non-Finnish) · 1,811/1,177,480 alleles

Filtering AF 0.148% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.146%

Overall 0.124% 1,992/1,610,096 alleles · rare

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.204%	491
European (non-Finnish)grpmax	0.154%	650
Admixed American	0.0552%	1,811
Finnishnot grpmax-eligible	0.0157%	6,379
African / African-American	0.012%	8,332
Ashkenazi Jewishnot grpmax-eligible	0.00339%	29,528
East Asian	0.00223%	44,798

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: CLASP2
Protein: p.Ile447=
Coding: c.1341A>T
MANE Select: NM_001365631
dbSNP: rs142035502
Type: single nucleotide variant
Location: chr3:33612048 (GRCh38)
Gene constraint: LOEUF 0.365 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 66.98 · 7 PDB
Residue 447: the 'disordered' region; the 'interaction with microtubules, mapre1 and mapre3' region

Full CLASP2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

CLASP2-related disorder

Similar variants

CLASP2 c.2240-4C>G Uncertain significance same condition
CLASP2 c.1694+8C>T Likely benign same condition
CLASP2 c.2455-1147C>G Benign same condition
CLASP2 p.Ala1461= Benign same condition
CLASP2 p.Asn872= Likely benign same condition
CLASP2 p.Asp1262= Likely benign same condition
CLASP2 p.Asp1442= Likely benign same condition
CLASP2 p.Glu2= Likely benign 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/clasp2-p-ile447 (accessed [today's date]).

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