Is CLASP2 p.Thr1107Ile (c.3320C>T) pathogenic?

CLASP2 p.Thr1107Ile (c.3320C>T) is classified Benign in CLASP2 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-03-15). AlphaMissense: likely benign (0.1625); Low-frequency (popmax 1.11%, mid); Associated with CLASP2-related disorder.

What condition is associated with CLASP2 p.Thr1107Ile (c.3320C>T)?

CLASP2 p.Thr1107Ile (c.3320C>T) is associated with CLASP2-related disorder (ClinVar).

How common is CLASP2 p.Thr1107Ile (c.3320C>T) in the general population?

CLASP2 p.Thr1107Ile (c.3320C>T) is low-frequency (popmax 1.11%, mid) (gnomAD).

What do computational predictors say about CLASP2 p.Thr1107Ile (c.3320C>T)?

AlphaMissense predicts likely benign (score 0.1625) — an in-silico prediction, not a clinical call.

CLASP2 p.Thr1107Ile

c.3320C>T · rs187113660 · VCV3056625

Benign No assertion criteria

Classification

Benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1625 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 1.11%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

CLASP2-related disorder

Computational evidence

Protein change
AlphaMissense	0.1625	likely benign
REVEL	0.275	benign-leaning
SaProt	LLR -7.32	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 12	GERP 2.2, phastCons 1
Regional constraint	o/e 0.74	unconstrained · MANE · 94 kb · p 3.9e-16 · regional, not allelic
Overall
CADD	24.7	PHRED · no single calibrated threshold — expert panels disagree

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

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM T895I vs ClinVar T1107I) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 1.11% Middle Eastern · 67/6,054 alleles

Filtering AF 0.894% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.817%

Overall 0.394% 6,352/1,611,652 alleles · low-frequency

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	1.43%	70
Middle Easterngrpmax	1.11%	90
Remaining individualsnot grpmax-eligible	0.556%	180
European (non-Finnish)	0.427%	234
South Asian	0.204%	489
Finnishnot grpmax-eligible	0.203%	492
Admixed American	0.193%	517
African / African-American	0.0707%	1,415

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: CLASP2
Protein: p.Thr1107Ile
Coding: c.3320C>T
MANE Select: NM_001365631
dbSNP: rs187113660
Type: single nucleotide variant
Location: chr3:33543517 (GRCh38)
Gene constraint: LOEUF 0.365 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 66.98 · 7 PDB
Residue 1107: an α-helix; the 'interaction with rsn and localization to the golgi and kinetochores' region; the 'required for cortical localization' 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-thr1107ile (accessed [today's date]).

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