Is EXT1 p.Arg86Ter (c.256C>T) pathogenic?

EXT1 p.Arg86Ter (c.256C>T) is classified Pathogenic/Likely pathogenic in EXT1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-07-24). Very rare (popmax 6.2e-05%); Associated with EXT1-related disorders.

What condition is associated with EXT1 p.Arg86Ter (c.256C>T)?

EXT1 p.Arg86Ter (c.256C>T) is associated with EXT1-related disorders, hereditary multiple osteochondromas (ClinVar).

How common is EXT1 p.Arg86Ter (c.256C>T) in the general population?

EXT1 p.Arg86Ter (c.256C>T) is very rare (popmax 6.2e-05%) (gnomAD).

EXT1 p.Arg86Ter

c.256C>T · rs760899584 · VCV2110297

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 6.2e-05%)

Conditions

EXT1-related disorders

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function in a haploinsufficient gene (ClinGen)
NMD	predicted	premature termination codon in exon 1 of 11
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.9	GERP 4.1, phastCons 1
Overall
CADD	41.0	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 6.2e-05%

Overall 6.2e-05% 1/1,613,590 alleles · very rare exomes 1/1,461,320 · genomes 0/152,270 · joint denominator

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.Arg86Ter
Coding: c.256C>T
MANE Select: NM_000127
dbSNP: rs760899584
Type: single nucleotide variant
Location: chr8:118110791 (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

EXT1-related disorders

Also linked: hereditary multiple osteochondromas

Similar variants

EXT1 p.Arg86= Likely benign ★ same residue
EXT1 c.1056+1G>A Pathogenic ★★ same condition
EXT1 c.1056+1G>T Pathogenic ★★ same condition
EXT1 c.1165-1G>A Pathogenic ★★ same condition
EXT1 c.1285-1G>C Pathogenic ★★ same condition
EXT1 c.1417+1G>A Pathogenic ★★ same condition
EXT1 c.1417+1G>T Pathogenic ★★ same condition
EXT1 c.1418-1G>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/ext1-p-arg86ter (accessed [today's date]).

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