Is EXT1 p.Arg6Leu (c.17G>T) pathogenic?

EXT1 p.Arg6Leu (c.17G>T) is classified Uncertain significance in EXT1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-13). AlphaMissense: likely pathogenic (0.7732); No allele count reported in gnomAD v4.1 (AN 1,598,248).

How common is EXT1 p.Arg6Leu (c.17G>T) in the general population?

EXT1 p.Arg6Leu (c.17G>T) is no allele count reported in gnomAD v4.1 (AN 1,598,248) (gnomAD).

What do computational predictors say about EXT1 p.Arg6Leu (c.17G>T)?

AlphaMissense predicts likely pathogenic (score 0.7732) — an in-silico prediction, not a clinical call.

EXT1 p.Arg6Leu

c.17G>T · VCV4881417

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7732 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,598,248)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.7732	likely pathogenic
REVEL	0.613	indeterminate
SaProt	LLR -5.33	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 5.8, phastCons 1
Regional constraint	o/e 1.10	unconstrained · MANE · 371 bp · p 0.2 · regional, not allelic
Overall
CADD	33.0	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

No allele count reported in gnomAD v4.1 (AN 1,598,248). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: EXT1
Protein: p.Arg6Leu
Coding: c.17G>T
MANE Select: NM_000127
Type: single nucleotide variant
Location: chr8:118111030 (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

Similar variants

EXT1 p.Arg6Gly Uncertain significance ★ ⚠ same residue
EXT1 p.Arg6Pro Uncertain significance ★ ⚠ same residue
EXT1 p.Arg6= Likely benign ★ same residue
EXT1 p.Arg6fs Pathogenic ★★ same residue
EXT1 c.1056+1G>A Pathogenic ★★ same type
EXT1 c.1056+1G>T Pathogenic ★★ same type
EXT1 c.1165-1G>A Pathogenic ★★ same type
EXT1 c.1285-1G>C Pathogenic ★★ same type

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-arg6leu (accessed [today's date]).

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