Is CLASP1 p.Thr730Arg (c.2189C>G) pathogenic?

CLASP1 p.Thr730Arg (c.2189C>G) is classified Uncertain significance in CLASP1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-10-29). AlphaMissense: likely pathogenic (0.7502); Absent from gnomAD v4.1.

How common is CLASP1 p.Thr730Arg (c.2189C>G) in the general population?

CLASP1 p.Thr730Arg (c.2189C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CLASP1 p.Thr730Arg (c.2189C>G)?

AlphaMissense predicts likely pathogenic (score 0.7502) — an in-silico prediction, not a clinical call.

CLASP1 p.Thr730Arg

c.2189C>G · VCV3493217

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7502 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.7502	likely pathogenic
REVEL	0.213	benign-leaning
SaProt	LLR -11.32	damaging
⇒ AlphaMissense and SaProt call this damaging; REVEL does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2, phastCons 1
Overall
CADD	26.9	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: CLASP1
Protein: p.Thr730Arg
Coding: c.2189C>G
MANE Select: NM_001395891
Type: single nucleotide variant
Location: chr2:121425162 (GRCh38)
Gene constraint: LOEUF 0.237 · pLI 1.00 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 69.44 · 3 PDB
Residue 730: the 'interaction with microtubules, mapre1 and mapre3' region; the 'disordered' region

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

Similar variants

CLASP1 c.196-567G>A Pathogenic/Likely pathogenic ★★ same type
CLASP1 c.196-570C>T Pathogenic/Likely pathogenic ★★ same type
CLASP1 c.196-594G>A Pathogenic/Likely pathogenic ★★ same type
CLASP1 c.196-605C>T Pathogenic/Likely pathogenic ★★ same type
CLASP1 c.196-670T>G Pathogenic/Likely pathogenic ★★ same type
CLASP1 n.30G>A Likely pathogenic ★★ same type
MAST1 p.Gly517Ser Pathogenic ★★ same type
MAST1 p.Pro1177Leu Likely pathogenic ★★ ⚠ 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/clasp1-p-thr730arg (accessed [today's date]).

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