Is EXTL3 p.Pro151Thr (c.451C>A) pathogenic?

EXTL3 p.Pro151Thr (c.451C>A) is classified Uncertain significance in EXTL3 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-10-16). AlphaMissense: likely pathogenic (0.7696); Absent from gnomAD v4.1.

How common is EXTL3 p.Pro151Thr (c.451C>A) in the general population?

EXTL3 p.Pro151Thr (c.451C>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about EXTL3 p.Pro151Thr (c.451C>A)?

AlphaMissense predicts likely pathogenic (score 0.7696) — an in-silico prediction, not a clinical call.

EXTL3 p.Pro151Thr

c.451C>A · rs1801150930 · VCV1466909

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7696 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.7696	likely pathogenic
REVEL	0.773	moderately pathogenic-leaning
SaProt	LLR -7.30	tolerated
⇒ AlphaMissense and REVEL call this damaging; SaProt does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 1.4, phastCons 1
Regional constraint	o/e 0.91	unconstrained · MANE · 1,803 bp · p 0.01 · regional, not allelic
Overall
CADD	24.8	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

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: EXTL3
Protein: p.Pro151Thr
Coding: c.451C>A
MANE Select: NM_001440
dbSNP: rs1801150930
Type: single nucleotide variant
Location: chr8:28716510 (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.Pro151Ser Uncertain significance ★★ ⚠ same residue
EXTL3 p.Pro318Leu Pathogenic/Likely pathogenic ★★ ⚠ same type
EXTL3 p.Ala373Thr Uncertain significance ★★ ⚠ same type
EXTL3 p.Ala385Val Uncertain significance ★★ ⚠ same type
EXTL3 p.Ala481Val Uncertain significance ★★ ⚠ same type
EXTL3 p.Ala482Thr Uncertain significance ★★ ⚠ same type
EXTL3 p.Ala507Ser Uncertain significance ★★ ⚠ same type
EXTL3 p.Ala560Ser 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-pro151thr (accessed [today's date]).

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