Is EXT2 p.Ala173= (c.519G>A) pathogenic?

EXT2 p.Ala173= (c.519G>A) is classified Benign/Likely benign in EXT2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-02-16). Ultra-rare (popmax 0.0174%, afr); Associated with exostoses, multiple, type 2.

What condition is associated with EXT2 p.Ala173= (c.519G>A)?

EXT2 p.Ala173= (c.519G>A) is associated with exostoses, multiple, type 2 (ClinVar).

How common is EXT2 p.Ala173= (c.519G>A) in the general population?

EXT2 p.Ala173= (c.519G>A) is ultra-rare (popmax 0.0174%, afr) (gnomAD).

How is Multiple osteochondromas inherited?

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

EXT2 p.Ala173=

c.519G>A · rs148121594 · VCV2726268

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0174%, afr)

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 -8.9	GERP -4.8
Overall
CADD	0.246	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0174% African / African-American · 13/74,924 alleles

Filtering AF 0.0103% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00813%

Overall 0.00167% 27/1,612,612 alleles · ultra-rare exomes 17/1,460,454 · genomes 10/152,158 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0174%	5,763
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,606
South Asian	0.0011%	91,078
European (non-Finnish)	0.00102%	98,333

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.Ala173=
Coding: c.519G>A
MANE Select: NM_207122
dbSNP: rs148121594
Type: single nucleotide variant
Location: chr11:44108231 (GRCh38)
Gene constraint: LOEUF 0.775 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 87.59 · 6 PDB
Residue 173: 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 p.Ala173Val Uncertain significance ★ ⚠ same residue
EXT2 p.Ala173fs Pathogenic ★ same residue
EXT2 p.Ala173Thr 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

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-ala173 (accessed [today's date]).

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