Is EXT2 p.Thr587= (c.1761G>A) pathogenic?

EXT2 p.Thr587= (c.1761G>A) is classified Benign/Likely benign in EXT2 (ClinVar, Multiple submitters, 5 submitters; last evaluated 2026-02-01). Low-frequency (popmax 4.57%, afr); Associated with exostoses, multiple, type 1.

What condition is associated with EXT2 p.Thr587= (c.1761G>A)?

EXT2 p.Thr587= (c.1761G>A) is associated with exostoses, multiple, type 1, exostoses, multiple, type 2 (ClinVar).

How common is EXT2 p.Thr587= (c.1761G>A) in the general population?

EXT2 p.Thr587= (c.1761G>A) is low-frequency (popmax 4.57%, afr) (gnomAD).

How is Multiple osteochondromas inherited?

Typically Autosomal dominant (Orphanet). A genetic counselor can assess individual risk for a family.

EXT2 p.Thr587=

c.1761G>A · rs16937864 · VCV304591

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

gnomAD v4.1

Rare

low-frequency (popmax 4.57%, afr)

Conditions

exostoses, multiple, type 1

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -5.8	GERP -4.4
Overall
CADD	2.398	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 4.57% African / African-American · 3,429/75,014 alleles

Filtering AF 4.44% ClinGen BA1/BS1 input FAF95, joint · FAF99 4.39%

Overall 0.258% 4,172/1,614,024 alleles · low-frequency exomes 2,152/1,461,760 · genomes 2,020/152,264 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	4.57%	22
Middle Eastern	0.512%	195
Admixed American	0.362%	277
Remaining individualsnot grpmax-eligible	0.35%	285
European (non-Finnish)	0.0219%	4,574
South Asian	0.0154%	6,505
Finnishnot grpmax-eligible	0.00625%	16,005

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: EXT2
Protein: p.Thr587=
Coding: c.1761G>A
MANE Select: NM_207122
dbSNP: rs16937864
Type: single nucleotide variant
Location: chr11:44232451 (GRCh38)
Gene constraint: LOEUF 0.775 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 87.59 · 6 PDB

Full EXT2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

exostoses, multiple, type 1 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: exostoses, multiple, type 2

For Multiple osteochondromas (Orphanet):

Inheritance: Autosomal dominant
Onset: Childhood
Prevalence: >1 / 1000 (Specific population)

Similar variants

EXT2 p.Thr587Met Conflicting classifications of pathogenicity ★ ⚠ same residue
EXT2 c.1079+1G>A Pathogenic ★★ same condition
EXT2 c.1079+1G>T Pathogenic ★★ same condition
EXT2 c.1173+1G>A Pathogenic ★★ same condition
EXT2 c.1662+1G>C Likely pathogenic ★★ same condition
EXT2 c.536+1G>A Pathogenic ★★ same condition
EXT2 c.626+1G>A Pathogenic ★★ same condition
EXT2 c.626+1G>C Pathogenic ★★ 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/ext2-p-thr587 (accessed [today's date]).

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