Is EXT1 p.Lys299= (c.897G>A) pathogenic?

EXT1 p.Lys299= (c.897G>A) is classified Likely benign in EXT1 (ClinVar, Single submitter, 1 submitter; last evaluated 2020-04-08). Very rare (popmax 0.000424%, nfe).

How common is EXT1 p.Lys299= (c.897G>A) in the general population?

EXT1 p.Lys299= (c.897G>A) is very rare (popmax 0.000424%, nfe) (gnomAD).

EXT1 p.Lys299=

c.897G>A · VCV4901509

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.000424%, nfe)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.13	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.64	GERP 1.8, phastCons 1
Overall
CADD	12.32	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000424% European (non-Finnish) · 5/1,180,036 alleles

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

Overall 0.00031% 5/1,614,196 alleles · very rare exomes 5/1,461,888 · genomes 0/152,308 · 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.Lys299=
Coding: c.897G>A
MANE Select: NM_000127
Type: single nucleotide variant
Location: chr8:118110150 (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.Lys299Glu Uncertain significance ★ ⚠ 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
EXT1 c.1417+1G>A Pathogenic ★★ same type
EXT1 c.1417+1G>T Pathogenic ★★ same type
EXT1 c.1418-1G>A 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-lys299 (accessed [today's date]).

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