Is CLASP1 p.Pro709Ser (c.2125C>T) pathogenic?

CLASP1 p.Pro709Ser (c.2125C>T) is classified Uncertain significance in CLASP1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-06-06). AlphaMissense: likely benign (0.0628); Ultra-rare (popmax 0.0165%, mid).

How common is CLASP1 p.Pro709Ser (c.2125C>T) in the general population?

CLASP1 p.Pro709Ser (c.2125C>T) is ultra-rare (popmax 0.0165%, mid) (gnomAD).

What do computational predictors say about CLASP1 p.Pro709Ser (c.2125C>T)?

AlphaMissense predicts likely benign (score 0.0628) — an in-silico prediction, not a clinical call.

CLASP1 p.Pro709Ser

c.2125C>T · rs958220718 · VCV2521021

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0628 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0165%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0628	likely benign
REVEL	0.086	moderately benign-leaning
SaProt	LLR -5.27	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 8.7	GERP 1.7, phastCons 1
Overall
CADD	23.8	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.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0165% Middle Eastern · 1/6,062 alleles

Filtering AF 2.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000411% 6/1,461,364 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0165%	6,062
Remaining individualsnot grpmax-eligible	0.0048%	20,824
European (non-Finnish)	0.00017%	589,894

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.Pro709Ser
Coding: c.2125C>T
MANE Select: NM_001395891
dbSNP: rs958220718
Type: single nucleotide variant
Location: chr2:121425226 (GRCh38)
Gene constraint: LOEUF 0.237 · pLI 1.00 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 69.44 · 3 PDB
Residue 709: 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

MAST1 p.Pro709Ala Uncertain significance ★ ⚠ same residue
MAST1 p.Pro709Leu Uncertain significance ★ ⚠ same residue
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

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-pro709ser (accessed [today's date]).

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