EXTL3 p.Pro171=
c.513G>A · rs35677003 · VCV1649335
Benign/Likely benign
Multiple submitters
Classification
Benign/Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
rare (popmax 0.555%, eas)
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 -1.5 | GERP -2.7 |
| Overall | ||
| CADD | 1.149 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.555%
East Asian · 249/44,888 alleles
Filtering AF
0.498%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.476%
Overall
0.0183%
295/1,614,144 alleles · rare
exomes 252/1,461,882 · genomes 43/152,262 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.555% | 180 |
| Remaining individualsnot grpmax-eligible | 0.016% | 6,250 |
| South Asian | 0.0143% | 7,007 |
| African / African-American | 0.012% | 8,338 |
| Admixed American | 0.0117% | 8,575 |
| European (non-Finnish) | 0.000593% | 168,575 |
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
- EXTL3
- Protein
- p.Pro171=
- Coding
- c.513G>A
- MANE Select
- NM_001440
- dbSNP
- rs35677003
- Type
- single nucleotide variant
- Location
- chr8:28716572 (GRCh38)
- Gene constraint
- LOEUF 0.511 · pLI 0.93 (gnomAD)
- Structure
- AlphaFold pLDDT 84.22 · 4 PDB
- Residue 171
- an α-helix
Similar variants
- EXTL3 p.Pro171Leu Uncertain significance ★★ ⚠ same residue
- EXTL3 p.Pro171Gln Uncertain significance ★ ⚠ same residue
- EXTL3 p.Pro171Ser 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
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-pro171 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown