OGFR p.Pro546=
c.1638A>G · rs3210217 · VCV2652500
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0501%, 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 -0.41 | GERP -0.86 |
| Overall | ||
| CADD | 3.7 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0501%
Middle Eastern · 2/3,994 alleles
Filtering AF
0.0159%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.013%
Overall
0.00827%
121/1,462,334 alleles · ultra-rare
exomes 49/1,352,864 · genomes 72/109,470 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.0501% | 1,997 |
| Finnishnot grpmax-eligible | 0.038% | 2,634 |
| African / African-American | 0.0255% | 3,920 |
| Admixed American | 0.018% | 5,566 |
| Ashkenazi Jewishnot grpmax-eligible | 0.0119% | 8,433 |
| East Asian | 0.0109% | 9,180 |
| South Asian | 0.00837% | 11,954 |
| Remaining individualsnot grpmax-eligible | 0.00541% | 18,487 |
| European (non-Finnish) | 0.00538% | 18,582 |
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
- OGFR
- Protein
- p.Pro546=
- Coding
- c.1638A>G
- MANE Select
- NM_007346
- dbSNP
- rs3210217
- Type
- single nucleotide variant
- Location
- chr20:62813253 (GRCh38)
- Gene constraint
- LOEUF 0.984 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 63.00
- Residue 546
- the 'disordered' region; the '7 x 20 aa approximate tandem repeats of [st]-p-s-e-t-p-g-p-[sr]-p-a-g-p-[at]-[gr]-d-e-p-a-[ek]' region
Similar variants
- OGFR p.Ala253Val Uncertain significance ★ ⚠ same type
- OGFR p.Ala411Thr Uncertain significance ★ ⚠ same type
- OGFR p.Ala469Thr Uncertain significance ★ ⚠ same type
- OGFR p.Ala480Val Uncertain significance ★ ⚠ same type
- OGFR p.Ala627Val Uncertain significance ★ ⚠ same type
- OGFR p.Ala655Thr Uncertain significance ★ ⚠ same type
- OGFR p.Ala660Val Uncertain significance ★ ⚠ same type
- OGFR p.Arg138Gln 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/ogfr-p-pro546 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown