Is EXT1 p.Pro476= (c.1428C>A) pathogenic?

EXT1 p.Pro476= (c.1428C>A) is classified Likely benign in EXT1 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-10-28). Absent from gnomAD v4.1.

How common is EXT1 p.Pro476= (c.1428C>A) in the general population?

EXT1 p.Pro476= (c.1428C>A) is absent from gnomAD v4.1 (gnomAD).

EXT1 p.Pro476=

c.1428C>A · VCV4901499

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

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 7.6	GERP 1.7, phastCons 1
Overall
CADD	11.27	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: EXT1
Protein: p.Pro476=
Coding: c.1428C>A
MANE Select: NM_000127
Type: single nucleotide variant
Location: chr8:117819784 (GRCh38)
Gene constraint: LOEUF 0.339 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 84.67 · 6 PDB
Residue 476: an α-helix

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

Similar variants

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
EXT1 c.1417+1G>A Pathogenic ★★ same type
EXT1 c.1417+1G>T Pathogenic ★★ same type
EXT1 c.1418-1G>A Pathogenic ★★ same type
EXT1 c.1418-2A>G 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-pro476 (accessed [today's date]).

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