Is EXTL3 p.Val291fs (c.743_870dup) pathogenic?

EXTL3 p.Val291fs (c.743870dup) is classified Uncertain significance in EXTL3 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-06-14). No gnomAD frequency available for this variant.

How common is EXTL3 p.Val291fs (c.743_870dup) in the general population?

EXTL3 p.Val291fs (c.743_870dup) is no gnomAD frequency available for this variant (gnomAD).

EXTL3 p.Val291fs

c.743_870dup · rs2486622295 · VCV2006672

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function in a LoF-intolerant gene
NMD	predicted	premature termination codon in exon 3 of 7
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 2.2	GERP -2.7, phastCons 1

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

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. 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: EXTL3
Protein: p.Val291fs
Coding: c.743_870dup
MANE Select: NM_001440
dbSNP: rs2486622295
Type: Duplication
Location: chr8:28716800 (GRCh38)
Gene constraint: LOEUF 0.511 · pLI 0.93 (gnomAD)
Structure: AlphaFold pLDDT 84.22 · 4 PDB

Full EXTL3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

EXTL3 p.Val291Ile Uncertain significance ★★ ⚠ same residue
EXTL3 c.2277-15_2277-3dup Likely benign ★★ same type
EXTL3 p.55DEA[3] Uncertain significance ★ same type
EXTL3 p.Glu351Ter Uncertain significance ★ same type
EXTL3 p.Gly3fs Uncertain significance ★ same type
EXTL3 p.Tyr670Ter Uncertain significance ★ 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/extl3-p-val291fs (accessed [today's date]).

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