TCOF1 p.Pro103=
c.309A>C · rs1209030910 · VCV1455191
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00534%, afr)
Conditions
1
Treacher Collins syndrome 1
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -0.52 | GERP -3.9 |
| Overall | ||
| CADD | 4.063 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00534%
African / African-American · 4/74,928 alleles
Filtering AF
0.00175%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00104%
Overall
0.000248%
4/1,614,066 alleles · very rare
exomes 2/1,461,850 · genomes 2/152,216 · joint denominator
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
- TCOF1
- Protein
- p.Pro103=
- Coding
- c.309A>C
- MANE Select
- NM_001371623
- dbSNP
- rs1209030910
- Type
- single nucleotide variant
- Location
- chr5:150367848 (GRCh38)
- Gene constraint
- LOEUF 0.288 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 41.78
- Residue 103
- the 'disordered' region
Similar variants
- TCOF1 p.Pro103Ala Uncertain significance ★ ⚠ same residue
- TCOF1 c.1278+1G>A Pathogenic ★★ same condition
- TCOF1 c.3047-1G>A Pathogenic ★★ same condition
- TCOF1 p.Arg288Ter Pathogenic/Likely pathogenic ★★ same condition
- TCOF1 p.Arg660Ter Pathogenic ★★ same condition
- TCOF1 p.Arg988Ter Pathogenic ★★ same condition
- TCOF1 p.Gln1164Ter Pathogenic ★★ same condition
- TCOF1 p.Gln402Ter 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/tcof1-p-pro103 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown