Is EXT2 p.Asp547= (c.1641C>T) pathogenic?

EXT2 p.Asp547= (c.1641C>T) is classified Benign in EXT2 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2026-01-24). Low-frequency (popmax 1.62%, eas); Associated with exostoses, multiple, type 2.

What condition is associated with EXT2 p.Asp547= (c.1641C>T)?

EXT2 p.Asp547= (c.1641C>T) is associated with exostoses, multiple, type 2 (ClinVar).

How common is EXT2 p.Asp547= (c.1641C>T) in the general population?

EXT2 p.Asp547= (c.1641C>T) is low-frequency (popmax 1.62%, eas) (gnomAD).

How is Multiple osteochondromas inherited?

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

EXT2 p.Asp547=

c.1641C>T · rs75987184 · VCV304590

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

low-frequency (popmax 1.62%, eas)

Conditions

exostoses, multiple, type 2

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 -11	GERP -3.5
Overall
CADD	0.375	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 1.62% East Asian · 727/44,866 alleles

Filtering AF 1.52% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.48%

Overall 0.0707% 1,141/1,614,058 alleles · low-frequency exomes 1,001/1,461,802 · genomes 140/152,256 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	1.62%	62
Remaining individualsnot grpmax-eligible	0.176%	568
Ashkenazi Jewishnot grpmax-eligible	0.0845%	1,184
African / African-American	0.04%	2,501
Middle Eastern	0.033%	3,031
South Asian	0.0242%	4,140
European (non-Finnish)	0.0186%	5,388
Admixed American	0.005%	20,007
Finnishnot grpmax-eligible	0.00469%	21,334

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.Asp547=
Coding: c.1641C>T
MANE Select: NM_207122
dbSNP: rs75987184
Type: single nucleotide variant
Location: chr11:44206938 (GRCh38)
Gene constraint: LOEUF 0.775 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 87.59 · 6 PDB
Residue 547: an α-helix

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

Disease context

exostoses, multiple, type 2 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Multiple osteochondromas (Orphanet):

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

Similar variants

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
EXT2 c.626+1G>T Pathogenic/Likely 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-asp547 (accessed [today's date]).

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