COL5A3 p.Pro496=
c.1488C>T · rs149416121 · VCV724669
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
rare (popmax 0.102%, mid)
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 -0.16 | GERP -3.3, phastCons 0.003 |
| Overall | ||
| CADD | 1.913 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.102%
Middle Eastern · 6/5,880 alleles
Filtering AF
0.0759%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0698%
Overall
0.0143%
226/1,580,160 alleles · rare
exomes 193/1,427,964 · genomes 33/152,196 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.102% | 980 |
| South Asian | 0.0923% | 1,084 |
| Admixed American | 0.0668% | 1,496 |
| Remaining individualsnot grpmax-eligible | 0.0295% | 3,387 |
| European (non-Finnish) | 0.00696% | 14,377 |
| African / African-American | 0.00543% | 18,413 |
| Finnishnot grpmax-eligible | 0.00318% | 31,495 |
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
- COL5A3
- Protein
- p.Pro496=
- Coding
- c.1488C>T
- MANE Select
- NM_015719
- dbSNP
- rs149416121
- Type
- single nucleotide variant
- Location
- chr19:9996111 (GRCh38)
- Gene constraint
- LOEUF 0.812 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 51.26
- Residue 496
- the 'triple-helical region' region; the 'disordered' region; the collagen-like 2 domain
Similar variants
- COL5A3 p.Arg1177Trp Uncertain significance ★★ ⚠ same type
- COL5A3 p.Asp855= Benign ★★ same type
- COL5A3 p.Phe178= Benign ★★ same type
- COL5A3 p.Pro1050Ser Benign ★★ same type
- COL5A3 p.Val1195Ala Benign ★★ same type
- COL5A3 p.Ala1005Thr Uncertain significance ★ ⚠ same type
- COL5A3 p.Ala1096Thr Uncertain significance ★ ⚠ same type
- COL5A3 p.Ala121Thr 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/col5a3-p-pro496 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown