Is CLASP2 p.Arg751His (c.2252G>A) pathogenic?

CLASP2 p.Arg751His (c.2252G>A) is classified Uncertain significance in CLASP2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-12-16). AlphaMissense: likely pathogenic (0.6882); Very rare (popmax 0.00534%, afr).

How common is CLASP2 p.Arg751His (c.2252G>A) in the general population?

CLASP2 p.Arg751His (c.2252G>A) is very rare (popmax 0.00534%, afr) (gnomAD).

What do computational predictors say about CLASP2 p.Arg751His (c.2252G>A)?

AlphaMissense predicts likely pathogenic (score 0.6882) — an in-silico prediction, not a clinical call.

CLASP2 p.Arg751His

c.2252G>A · VCV3833689

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6882 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00534%, afr)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.6882	likely pathogenic
REVEL	0.26	benign-leaning
SaProt	LLR -10.01	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 7.7	GERP 2.5, phastCons 1
Regional constraint	o/e 0.74	unconstrained · MANE · 94 kb · p 3.9e-16 · regional, not allelic
Overall
CADD	33.0	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 R518H vs ClinVar R751H) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00534% African / African-American · 4/74,904 alleles

Filtering AF 0.00175% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00104%

Overall 0.00143% 23/1,612,530 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00534%	18,726
Remaining individualsnot grpmax-eligible	0.0032%	31,210
East Asian	0.00223%	44,900
European (non-Finnish)	0.00127%	78,600
South Asian	0.0011%	90,842

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.Arg751His
Coding: c.2252G>A
MANE Select: NM_001365631
Type: single nucleotide variant
Location: chr3:33581916 (GRCh38)
Gene constraint: LOEUF 0.365 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 66.98 · 7 PDB
Residue 751: the 'tog 2' region

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.Ala1402Val 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-arg751his (accessed [today's date]).

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