Is EXT1 p.Arg36Trp (c.106C>T) pathogenic?

EXT1 p.Arg36Trp (c.106C>T) is classified Conflicting classifications of pathogenicity in EXT1 (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2023-06-01). AlphaMissense: likely benign (0.1184); Very rare (popmax 0.00223%, eas); Associated with chondrosarcoma.

What condition is associated with EXT1 p.Arg36Trp (c.106C>T)?

EXT1 p.Arg36Trp (c.106C>T) is associated with chondrosarcoma, ovarian cancer (ClinVar).

How common is EXT1 p.Arg36Trp (c.106C>T) in the general population?

EXT1 p.Arg36Trp (c.106C>T) is very rare (popmax 0.00223%, eas) (gnomAD).

How is Chondrosarcoma inherited?

Typically Not applicable, Unknown (Orphanet). A genetic counselor can assess individual risk for a family.

What do computational predictors say about EXT1 p.Arg36Trp (c.106C>T)?

AlphaMissense predicts likely benign (score 0.1184) — an in-silico prediction, not a clinical call.

EXT1 p.Arg36Trp

c.106C>T · rs770352704 · VCV2445271

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1184 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00223%, eas)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

chondrosarcoma

Computational evidence

Protein change
AlphaMissense	0.1184	likely benign
REVEL	0.489	indeterminate
SaProt	LLR -7.14	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL is indeterminate.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 7.9	GERP 5.6, phastCons 1
Regional constraint	o/e 1.10	unconstrained · MANE · 371 bp · p 0.2 · regional, not allelic
Overall
CADD	23.8	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 0.00223% East Asian · 1/44,882 alleles

Filtering AF 0.000124% ClinGen BA1/BS1 input FAF95, joint · FAF99 9e-05%

Overall 0.000372% 6/1,613,512 alleles · very rare exomes 5/1,461,392 · genomes 1/152,120 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00223%	44,882
European (non-Finnish)	0.000424%	236,010

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: EXT1
Protein: p.Arg36Trp
Coding: c.106C>T
MANE Select: NM_000127
dbSNP: rs770352704
Type: single nucleotide variant
Location: chr8:118110941 (GRCh38)
Gene constraint: LOEUF 0.339 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 84.67 · 6 PDB

Full EXT1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

chondrosarcoma — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: ovarian cancer

For Chondrosarcoma (Orphanet):

Inheritance: Not applicable, Unknown
Onset: Adult
Prevalence: 1-9 / 1 000 000 (Europe)

Similar variants

EXT1 p.Arg340Cys Pathogenic/Likely pathogenic ★★ same condition
EXT1 p.Arg340Leu Pathogenic ★★ same condition
EXT1 p.Gln2Ter Pathogenic ★★ same condition
EXT1 p.Ala689Thr Uncertain significance ★★ ⚠ same condition
EXT1 p.Arg188Ser Uncertain significance ★★ ⚠ same condition
EXT1 p.Arg325Trp Uncertain significance ★★ ⚠ same condition
EXT1 p.Arg384Lys Uncertain significance ★★ ⚠ same condition
EXT1 p.Arg691His Uncertain significance ★★ ⚠ 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/ext1-p-arg36trp (accessed [today's date]).

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