Is TSPEAR p.Pro150= (c.450G>A) pathogenic?

TSPEAR p.Pro150= (c.450G>A) is classified Likely benign in TSPEAR (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-11-07). Ultra-rare (popmax 0.0107%, afr); Associated with Inborn genetic diseases.

What condition is associated with TSPEAR p.Pro150= (c.450G>A)?

TSPEAR p.Pro150= (c.450G>A) is associated with Inborn genetic diseases (ClinVar).

How common is TSPEAR p.Pro150= (c.450G>A) in the general population?

TSPEAR p.Pro150= (c.450G>A) is ultra-rare (popmax 0.0107%, afr) (gnomAD).

TSPEAR p.Pro150=

c.450G>A · rs782696528 · VCV682345

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0107%, afr)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -4.5	GERP -2.8
Overall
CADD	0.932	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0107% African / African-American · 8/74,916 alleles

Filtering AF 0.00528% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00381%

Overall 0.00192% 31/1,612,322 alleles · ultra-rare exomes 27/1,460,164 · genomes 4/152,158 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0107%	9,365
Admixed American	0.00333%	29,991
South Asian	0.00329%	30,357
European (non-Finnish)	0.00153%	65,548

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: TSPEAR
Protein: p.Pro150=
Coding: c.450G>A
MANE Select: NM_144991
dbSNP: rs782696528
Type: single nucleotide variant
Location: chr21:44533777 (GRCh38)
Gene constraint: LOEUF 1.161 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 87.47
Residue 150: the laminin g-like domain

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

TSPEAR p.Pro150Leu Uncertain significance ★★ ⚠ same residue
TSPEAR c.1337-2A>G Likely pathogenic ★★ same condition
TSPEAR p.Ala166Thr Uncertain significance ★★ ⚠ same condition
TSPEAR p.Ala225Thr Uncertain significance ★★ ⚠ same condition
TSPEAR p.Ala352Thr Uncertain significance ★★ ⚠ same condition
TSPEAR p.Ala424Thr Uncertain significance ★★ ⚠ same condition
TSPEAR p.Ala439Glu Uncertain significance ★★ ⚠ same condition
TSPEAR p.Ala44Val Uncertain significance ★★ ⚠ same condition

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/tspear-p-pro150 (accessed [today's date]).

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