Is CLASP2 p.Ala1402Val (c.4205C>T) pathogenic?

CLASP2 p.Ala1402Val (c.4205C>T) is classified Uncertain significance in CLASP2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-20). AlphaMissense: likely pathogenic (0.8743); Very rare (popmax 0.000254%, nfe).

How common is CLASP2 p.Ala1402Val (c.4205C>T) in the general population?

CLASP2 p.Ala1402Val (c.4205C>T) is very rare (popmax 0.000254%, nfe) (gnomAD).

What do computational predictors say about CLASP2 p.Ala1402Val (c.4205C>T)?

AlphaMissense predicts likely pathogenic (score 0.8743) — an in-silico prediction, not a clinical call.

CLASP2 p.Ala1402Val

c.4205C>T · VCV4229345

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8743 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000254%, nfe)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.8743	likely pathogenic
REVEL	0.448	indeterminate
SaProt	LLR -9.20	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call.
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	28.2	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 A1190V vs ClinVar A1402V) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000254% European (non-Finnish) · 3/1,179,818 alleles

Filtering AF 6.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.9e-05%

Overall 0.000205% 3/1,461,560 alleles · very rare

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.Ala1402Val
Coding: c.4205C>T
MANE Select: NM_001365631
Type: single nucleotide variant
Location: chr3:33510670 (GRCh38)
Gene constraint: LOEUF 0.365 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 66.98 · 7 PDB

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.Ala1496Pro 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-ala1402val (accessed [today's date]).

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