Is CLASP1 p.Pro1287= (c.3861G>A) pathogenic?

CLASP1 p.Pro1287= (c.3861G>A) is classified Likely benign in CLASP1 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-05-28). Ultra-rare (popmax 0.0164%, mid); Associated with CLASP1-related disorder.

What condition is associated with CLASP1 p.Pro1287= (c.3861G>A)?

CLASP1 p.Pro1287= (c.3861G>A) is associated with CLASP1-related disorder (ClinVar).

How common is CLASP1 p.Pro1287= (c.3861G>A) in the general population?

CLASP1 p.Pro1287= (c.3861G>A) is ultra-rare (popmax 0.0164%, mid) (gnomAD).

CLASP1 p.Pro1287=

c.3861G>A · rs553380975 · VCV3043713

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0164%, mid)

Conditions

CLASP1-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>A here scores Δ0.32 · evaluated, not missing
Constraint at this position
Conservation	phyloP -7.9	GERP -4.2
Overall
CADD	3.362	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0164% Middle Eastern · 1/6,082 alleles

Filtering AF 0.00478% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00439%

Overall 0.00601% 97/1,613,888 alleles · ultra-rare

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	0.0439%	2,278
Middle Easterngrpmax	0.0164%	6,082
Remaining individualsnot grpmax-eligible	0.0064%	15,616
European (non-Finnish)	0.00593%	16,856
East Asian	0.00446%	22,443
South Asian	0.00439%	22,771
Admixed American	0.00167%	60,004
Finnishnot grpmax-eligible	0.00156%	64,014
African / African-American	0.00133%	74,924

Ashkenazi Jewish 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: CLASP1
Protein: p.Pro1287=
Coding: c.3861G>A
MANE Select: NM_001395891
dbSNP: rs553380975
Type: single nucleotide variant
Location: chr2:121367676 (GRCh38)
Gene constraint: LOEUF 0.237 · pLI 1.00 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 69.44 · 3 PDB
Residue 1287: the 'interaction with clip2' region; the 'interaction with phldb2 and rsn' region; the 'localization to kinetochores' region

Full CLASP1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

CLASP1-related disorder

Similar variants

CLASP1 p.Pro1287Leu Likely benign same residue
CLASP1 c.196-567G>A Pathogenic/Likely pathogenic ★★ same condition
CLASP1 c.196-594G>A Pathogenic/Likely pathogenic ★★ same condition
CLASP1 c.196-605C>T Pathogenic/Likely pathogenic ★★ same condition
CLASP1 n.30G>A Likely pathogenic ★★ same condition
RNU4ATAC n.53C>G Pathogenic/Likely pathogenic ★★ same condition
RNU4ATAC n.55G>A Pathogenic ★★ same condition
MAST1 p.Gln1392His 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/clasp1-p-pro1287 (accessed [today's date]).

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