Is CLASP1 p.Ser229Cys (c.686C>G) pathogenic?

CLASP1 p.Ser229Cys (c.686C>G) is classified Uncertain significance in CLASP1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-06). AlphaMissense: likely benign (0.1971); Ultra-rare (popmax 0.0137%, afr).

How common is CLASP1 p.Ser229Cys (c.686C>G) in the general population?

CLASP1 p.Ser229Cys (c.686C>G) is ultra-rare (popmax 0.0137%, afr) (gnomAD).

What do computational predictors say about CLASP1 p.Ser229Cys (c.686C>G)?

AlphaMissense predicts likely benign (score 0.1971) — an in-silico prediction, not a clinical call.

CLASP1 p.Ser229Cys

c.686C>G · VCV4654050

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1971 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0137%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1971	likely benign
REVEL	0.141	moderately benign-leaning
SaProt	LLR -8.70	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 1.6, phastCons 1
Overall
CADD	25.8	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0137% African / African-American · 10/73,104 alleles

Filtering AF 0.00739% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00562%

Overall 0.000774% 12/1,550,440 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0137%	7,310
European (non-Finnish)	0.000175%	572,787

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: CLASP1
Protein: p.Ser229Cys
Coding: c.686C>G
MANE Select: NM_001395891
Type: single nucleotide variant
Location: chr2:121503193 (GRCh38)
Gene constraint: LOEUF 0.237 · pLI 1.00 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 69.44 · 3 PDB

Full CLASP1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CLASP1 c.196-567G>A Pathogenic/Likely pathogenic ★★ same type
CLASP1 c.196-570C>T Pathogenic/Likely pathogenic ★★ same type
CLASP1 c.196-594G>A Pathogenic/Likely pathogenic ★★ same type
CLASP1 c.196-605C>T Pathogenic/Likely pathogenic ★★ same type
CLASP1 c.196-670T>G Pathogenic/Likely pathogenic ★★ same type
CLASP1 n.30G>A Likely pathogenic ★★ same type
MAST1 p.Gly517Ser Pathogenic ★★ same type
MAST1 p.Pro1177Leu Likely pathogenic ★★ ⚠ 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/clasp1-p-ser229cys (accessed [today's date]).

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