Is CLASP1 p.Phe220Val (c.658T>G) pathogenic?

CLASP1 p.Phe220Val (c.658T>G) is classified Uncertain significance in CLASP1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-21). AlphaMissense: likely pathogenic (0.9663); Ultra-rare (popmax 0.0138%, nfe).

How common is CLASP1 p.Phe220Val (c.658T>G) in the general population?

CLASP1 p.Phe220Val (c.658T>G) is ultra-rare (popmax 0.0138%, nfe) (gnomAD).

What do computational predictors say about CLASP1 p.Phe220Val (c.658T>G)?

AlphaMissense predicts likely pathogenic (score 0.9663) — an in-silico prediction, not a clinical call.

CLASP1 p.Phe220Val

c.658T>G · VCV4229316

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9663 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0138%, nfe)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9663	likely pathogenic
REVEL	0.171	moderately benign-leaning
SaProt	LLR -8.81	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 11	GERP 1.6, phastCons 1
Overall
CADD	26.7	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0138% European (non-Finnish) · 157/1,133,584 alleles

Filtering AF 0.012% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0114%

Overall 0.0119% 183/1,537,022 alleles · ultra-rare

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0184%	5,420
Finnishnot grpmax-eligible	0.0184%	5,448
European (non-Finnish)grpmax	0.0138%	7,220
African / African-American	0.00549%	18,203

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Phe220Val
Coding: c.658T>G
MANE Select: NM_001395891
Type: single nucleotide variant
Location: chr2:121503221 (GRCh38)
Gene constraint: LOEUF 0.237 · pLI 1.00 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 69.44 · 3 PDB
Residue 220: an α-helix

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-phe220val (accessed [today's date]).

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