OFD1 p.Ser736Phe
c.2207C>T · VCV3360493
Uncertain significance
Single submitter
Classification
Uncertain significance
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
AlphaMissense
likely pathogenic
0.6196 · ACMG-weighted
gnomAD v4.1
Absent
absent from gnomAD v4.1
Missense predictors
1/2 damaging
AlphaMissense, SaProt · REVEL indeterminate
Computational evidence
| Protein change | ||
| AlphaMissense | 0.6196 | likely pathogenic · top 5% in OFD1 |
|---|---|---|
| REVEL | 0.598 | indeterminate |
| SaProt | LLR -8.37 | tolerated |
| ⇒ AlphaMissense calls this damaging; SaProt does not; REVEL is indeterminate. | ||
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 3.3 | GERP 6.8, phastCons 0.99 |
| Regional constraint | o/e 1.02 | unconstrained · MANE · 8,639 bp · p 0.77 · regional, not allelic |
| Overall | ||
| CADD | 23.2 | 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
- OFD1
- Protein
- p.Ser736Phe
- Coding
- c.2207C>T
- MANE Select
- NM_003611
- Type
- single nucleotide variant
- Location
- chrX:13760667 (GRCh38)
- Structure
- AlphaFold pLDDT 68.41
- Residue 736
- the 'mediates the interaction with sdccag8' region; the 'disordered' region
Similar variants
- OFD1 c.1411+1G>A Pathogenic ★★ same type
- OFD1 c.2600-1G>C Pathogenic/Likely pathogenic ★★ same type
- OFD1 c.655-8A>G Likely pathogenic ★★ same type
- OFD1 p.Arg367Ter Pathogenic ★★ same type
- OFD1 p.Arg41Ter Pathogenic ★★ same type
- OFD1 p.Arg890Ter Pathogenic/Likely pathogenic ★★ same type
- OFD1 p.Arg909Ter Pathogenic/Likely pathogenic ★★ same type
- OFD1 p.Gln966Ter Pathogenic/Likely pathogenic ★★ 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/ofd1-p-ser736phe (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown