TTC7A p.Ser223=
c.669G>A · rs777759191 · VCV1092489
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00223%, eas)
Conditions
1
multiple intestinal atresia
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 -6.3 | |
| Overall | ||
| CADD | 0.465 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00223%
East Asian · 1/44,872 alleles
Filtering AF
0.00145%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00123%
Overall
0.00186%
30/1,613,776 alleles · very rare
exomes 28/1,461,736 · genomes 2/152,040 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.00223% | 44,872 |
| South Asian | 0.0022% | 45,534 |
| European (non-Finnish) | 0.00212% | 47,197 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,478 |
| African / African-American | 0.00134% | 74,870 |
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
- TTC7A
- Protein
- p.Ser223=
- Coding
- c.669G>A
- MANE Select
- NM_020458
- dbSNP
- rs777759191
- Type
- single nucleotide variant
- Location
- chr2:46978812 (GRCh38)
- Gene constraint
- LOEUF 1.198 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
- Structure
- AlphaFold pLDDT 84.59
Similar variants
- TTC7A p.Ser223Leu Uncertain significance ★★ ⚠ same residue
- TTC7A c.1288-1G>T Pathogenic/Likely pathogenic ★★ same condition
- TTC7A c.1641+1G>A Likely pathogenic ★★ same condition
- TTC7A c.2018-1G>C Pathogenic/Likely pathogenic ★★ same condition
- TTC7A p.Arg138Ter Pathogenic/Likely pathogenic ★★ same condition
- TTC7A p.Arg358Ter Pathogenic/Likely pathogenic ★★ same condition
- TTC7A p.Arg405Ter Pathogenic/Likely pathogenic ★★ same condition
- TTC7A p.Cys623Ter 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/ttc7a-p-ser223 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown