Is CLASP2 p.Phe1305Cys (c.3914T>G) pathogenic?

CLASP2 p.Phe1305Cys (c.3914T>G) is classified Uncertain significance in CLASP2 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-12-20). AlphaMissense: ambiguous (0.3751); Very rare (popmax 0.00186%, nfe).

How common is CLASP2 p.Phe1305Cys (c.3914T>G) in the general population?

CLASP2 p.Phe1305Cys (c.3914T>G) is very rare (popmax 0.00186%, nfe) (gnomAD).

What do computational predictors say about CLASP2 p.Phe1305Cys (c.3914T>G)?

AlphaMissense predicts ambiguous (score 0.3751) — an in-silico prediction, not a clinical call.

CLASP2 p.Phe1305Cys

c.3914T>G · rs748075075 · VCV2391260

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3751 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00186%, nfe)

Computational evidence

Protein change
AlphaMissense	0.3751	ambiguous
REVEL	0.414	indeterminate
SaProt	LLR -5.87	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.3	GERP 2.4, phastCons 1
Regional constraint	o/e 0.74	unconstrained · MANE · 94 kb · p 3.9e-16 · regional, not allelic
Overall
CADD	25.0	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 F1093C vs ClinVar F1305C) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00186% European (non-Finnish) · 22/1,179,786 alleles

Filtering AF 0.00122% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00104%

Overall 0.00143% 23/1,613,604 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00186%	53,627
Remaining individualsnot grpmax-eligible	0.0016%	62,452

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.Phe1305Cys
Coding: c.3914T>G
MANE Select: NM_001365631
dbSNP: rs748075075
Type: single nucleotide variant
Location: chr3:33517048 (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.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-phe1305cys (accessed [today's date]).

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