Is CLASP2 p.Val607Met (c.1819G>A) pathogenic?

CLASP2 p.Val607Met (c.1819G>A) is classified Uncertain significance in CLASP2 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-11-08). AlphaMissense: likely pathogenic (0.767); Very rare (popmax 8.52e-05%, nfe).

How common is CLASP2 p.Val607Met (c.1819G>A) in the general population?

CLASP2 p.Val607Met (c.1819G>A) is very rare (popmax 8.52e-05%, nfe) (gnomAD).

What do computational predictors say about CLASP2 p.Val607Met (c.1819G>A)?

AlphaMissense predicts likely pathogenic (score 0.767) — an in-silico prediction, not a clinical call.

CLASP2 p.Val607Met

c.1819G>A · rs2072729519 · VCV2324369

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.767 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.52e-05%, nfe)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.767	likely pathogenic
REVEL	0.192	benign-leaning
SaProt	LLR -6.82	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 2.3, phastCons 1
Regional constraint	o/e 0.97	unconstrained · MANE · 14 kb · p 0.71 · regional, not allelic
Overall
CADD	28.5	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 V374M vs ClinVar V607M) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.52e-05% European (non-Finnish) · 1/1,173,856 alleles

Overall 6.9e-05% 1/1,449,350 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.Val607Met
Coding: c.1819G>A
MANE Select: NM_001365631
dbSNP: rs2072729519
Type: single nucleotide variant
Location: chr3:33603057 (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 p.Val607Leu Uncertain significance ★ ⚠ same residue
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

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-val607met (accessed [today's date]).

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