Is CLASP2 p.Val487Ile (c.1459G>A) pathogenic?

CLASP2 p.Val487Ile (c.1459G>A) is classified Uncertain significance in CLASP2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-16). AlphaMissense: likely benign (0.1113); Very rare (popmax 0.00448%, sas).

How common is CLASP2 p.Val487Ile (c.1459G>A) in the general population?

CLASP2 p.Val487Ile (c.1459G>A) is very rare (popmax 0.00448%, sas) (gnomAD).

What do computational predictors say about CLASP2 p.Val487Ile (c.1459G>A)?

AlphaMissense predicts likely benign (score 0.1113) — an in-silico prediction, not a clinical call.

CLASP2 p.Val487Ile

c.1459G>A · rs370720523 · VCV3145297

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1113 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00448%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1113	likely benign
REVEL	0.144	moderately benign-leaning
SaProt	LLR -7.07	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 7.6	GERP 2.5, phastCons 1
Regional constraint	o/e 0.62	unconstrained · MANE · 38 kb · p 8.3e-12 · regional, not allelic
Overall
CADD	27.6	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.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM V254I vs ClinVar V487I) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00448% South Asian · 4/89,296 alleles

Filtering AF 0.00145% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000905%

Overall 0.00149% 24/1,605,904 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00448%	22,324
Ashkenazi Jewishnot grpmax-eligible	0.0034%	29,412
African / African-American	0.00268%	37,341
Admixed American	0.0017%	58,910
Remaining individualsnot grpmax-eligible	0.00161%	62,098
European (non-Finnish)	0.00128%	78,411

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.Val487Ile
Coding: c.1459G>A
MANE Select: NM_001365631
dbSNP: rs370720523
Type: single nucleotide variant
Location: chr3:33607451 (GRCh38)
Gene constraint: LOEUF 0.365 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 66.98 · 7 PDB
Residue 487: the 'interaction with microtubules, mapre1 and mapre3' region

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

Similar variants

CLASP2 c.1949-9C>T Benign ★★ same type
CLASP2 p.Gly57= Benign ★★ same type
CLASP2 p.Ser544= Benign ★★ same type
CLASP2 c.2068+1G>A Uncertain significance ★ same type
CLASP2 c.2455-1137A>C Uncertain significance ★ same type
CLASP2 p.Ala1209Gly Uncertain significance ★ ⚠ same type
CLASP2 p.Ala1251Pro Uncertain significance ★ ⚠ same type
CLASP2 p.Ala1402Val 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/clasp2-p-val487ile (accessed [today's date]).

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