Is EXT2 p.Arg10= (c.28C>A) pathogenic?

EXT2 p.Arg10= (c.28C>A) is classified Benign in EXT2 (ClinVar, Multiple submitters, 8 submitters; last evaluated 2026-02-04). Common (popmax 25.4%, eas) — too common for a highly-penetrant pathogenic allele; Associated with exostoses, multiple, type 1.

What condition is associated with EXT2 p.Arg10= (c.28C>A)?

EXT2 p.Arg10= (c.28C>A) is associated with exostoses, multiple, type 1, exostoses, multiple, type 2 (ClinVar).

How is Multiple osteochondromas inherited?

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

EXT2 p.Arg10=

Q: How common is EXT2 p.Arg10= (c.28C>A) in the general population?

EXT2 p.Arg10= (c.28C>A) is common (popmax 25.4%, eas) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.28C>A · rs4755228 · VCV195445

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 8 submitters

gnomAD v4.1

Common

common (popmax 25.4%, eas) — too common for a highly-penetrant pathogenic allele

Conditions

exostoses, multiple, type 1

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 5.9	GERP 1.4, phastCons 1
Overall
CADD	13.33	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 25.4% East Asian · 11,394/44,868 alleles

Filtering AF 25% ClinGen BA1/BS1 input FAF95, joint · FAF99 24.8%

Overall 1.56% 25,239/1,614,126 alleles · common exomes 22,314/1,461,874 · genomes 2,925/152,252 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	25.4%	4
South Asian	4.63%	22
Admixed American	3.44%	29
Remaining individualsnot grpmax-eligible	2.12%	47
Finnishnot grpmax-eligible	1.49%	67
Ashkenazi Jewishnot grpmax-eligible	0.622%	161
Middle Eastern	0.528%	189
African / African-American	0.407%	246
European (non-Finnish)	0.404%	248

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.Arg10=
Coding: c.28C>A
MANE Select: NM_207122
dbSNP: rs4755228
Type: single nucleotide variant
Location: chr11:44107740 (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.Arg10Gln Uncertain significance ★★ ⚠ same residue
EXT2 p.Arg10Trp Uncertain significance ★★ ⚠ 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

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-arg10 (accessed [today's date]).

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