Is EXT2 p.Ala202Val (c.605C>T) pathogenic?

EXT2 p.Ala202Val (c.605C>T) is classified Conflicting classifications of pathogenicity in EXT2 (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2024-12-02). AlphaMissense: likely benign (0.3203); Rare (popmax 0.136%, eas); Associated with exostoses, multiple, type 2.

What condition is associated with EXT2 p.Ala202Val (c.605C>T)?

EXT2 p.Ala202Val (c.605C>T) is associated with exostoses, multiple, type 2 (ClinVar).

How common is EXT2 p.Ala202Val (c.605C>T) in the general population?

EXT2 p.Ala202Val (c.605C>T) is rare (popmax 0.136%, eas) (gnomAD).

How is Multiple osteochondromas inherited?

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

What do computational predictors say about EXT2 p.Ala202Val (c.605C>T)?

AlphaMissense predicts likely benign (score 0.3203) — an in-silico prediction, not a clinical call.

EXT2 p.Ala202Val

c.605C>T · rs771803942 · VCV879931

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.3203 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.136%, eas)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

exostoses, multiple, type 2

Computational evidence

Protein change
AlphaMissense	0.3203	likely benign
REVEL	0.64	indeterminate
SaProt	LLR -4.27	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 2.7, phastCons 1
Regional constraint	o/e 0.93	unconstrained · MANE · 99 kb · p 0.085 · regional, not allelic
Overall
CADD	21.1	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.136% East Asian · 61/44,886 alleles

Filtering AF 0.109% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0986%

Overall 0.0039% 63/1,614,102 alleles · rare exomes 60/1,461,796 · genomes 3/152,306 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.136%	736
Remaining individualsnot grpmax-eligible	0.0032%	31,253

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.Ala202Val
Coding: c.605C>T
MANE Select: NM_207122
dbSNP: rs771803942
Type: single nucleotide variant
Location: chr11:44109262 (GRCh38)
Gene constraint: LOEUF 0.775 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 87.59 · 6 PDB
Residue 202: a UniProt-annotated variant site (in ext2)

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-ala202val (accessed [today's date]).

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