OFD1 p.His272=
c.816C>T · rs748363967 · VCV1636646
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00591%, eas)
Conditions
2
Joubert syndrome
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal. | ||
| Splicing | ||
| SpliceAI | Δ0.26 | donor loss · deltas |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -0.026 | GERP -4.8, phastCons 0.021 |
| Overall | ||
| CADD | 0.043 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00591%
East Asian · 2/33,842 alleles
Filtering AF
0.000979%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000366%
Overall
0.000821%
9/1,096,462 alleles · very rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.00591% | 16,921 |
| Remaining individualsnot grpmax-eligible | 0.0042% | 23,790 |
| South Asian | 0.00176% | 56,962 |
| European (non-Finnish) | 0.000447% | 223,496 |
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
- OFD1
- Protein
- p.His272=
- Coding
- c.816C>T
- MANE Select
- NM_003611
- dbSNP
- rs748363967
- Type
- single nucleotide variant
- Location
- chrX:13746941 (GRCh38)
- Structure
- AlphaFold pLDDT 68.41
Similar variants
- OFD1 p.His272Arg Uncertain significance ★★ ⚠ same residue
- OFD1 c.1411+1G>A Pathogenic ★★ same condition
- OFD1 c.2600-1G>C Pathogenic/Likely pathogenic ★★ same condition
- OFD1 p.Arg367Ter Pathogenic ★★ same condition
- OFD1 p.Arg41Ter Pathogenic ★★ same condition
- OFD1 p.Arg890Ter Pathogenic/Likely pathogenic ★★ same condition
- OFD1 p.Arg909Ter Pathogenic/Likely pathogenic ★★ same condition
- OFD1 p.Tyr87Cys Pathogenic ★★ ⚠ same condition
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/ofd1-p-his272 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown