Is EXT1 p.Arg340= (c.1020C>T) pathogenic?

EXT1 p.Arg340= (c.1020C>T) is classified Benign in EXT1 (ClinVar, Single submitter, 1 submitter). Very rare (popmax 8.47e-05%, nfe).

How common is EXT1 p.Arg340= (c.1020C>T) in the general population?

EXT1 p.Arg340= (c.1020C>T) is very rare (popmax 8.47e-05%, nfe) (gnomAD).

EXT1 p.Arg340=

c.1020C>T · rs886038242 · VCV255168

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 8.47e-05%, nfe)

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 9.9	GERP 1.7, phastCons 1
Overall
CADD	14.72	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.47e-05% European (non-Finnish) · 1/1,179,982 alleles

Overall 6.2e-05% 1/1,613,924 alleles · very rare exomes 0/1,461,778 · genomes 1/152,146 · 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.Arg340=
Coding: c.1020C>T
MANE Select: NM_000127
dbSNP: rs886038242
Type: single nucleotide variant
Location: chr8:117837144 (GRCh38)
Gene constraint: LOEUF 0.339 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 84.67 · 6 PDB
Residue 340: a UniProt-annotated variant site (in ext1; decreased glucuronosyl-n-acetylglucosaminyl-proteoglycan 4-alpha-n-acetylglucosaminyltransferase activity; decreased n-acetylglucosaminyl-proteoglycan 4-beta-glucuronosyltransferase activity; loss of heparan sulfate proteoglycan biosynthetic process; no effect on interaction with ext2; can be integrated in heparan sulfate polymerase complex); a UniProt-annotated variant site (in ext1); a UniProt-annotated variant site (in ext1; loss of heparan sulfate proteoglycan biosynthetic process); a β-strand

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

Similar variants

EXT1 p.Arg340Cys Pathogenic/Likely pathogenic ★★ same residue
EXT1 p.Arg340Gly Pathogenic/Likely pathogenic ★★ same residue
EXT1 p.Arg340His Pathogenic ★★ ⚠ same residue
EXT1 p.Arg340Leu 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-arg340 (accessed [today's date]).

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