TTC7A p.Ala528=
c.1584G>A · rs761294322 · VCV528476
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
very rare (popmax 0.00434%, nfe)
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 -7.1 | GERP -3.9 |
| Overall | ||
| CADD | 0.147 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00434%
European (non-Finnish) · 51/1,176,182 alleles
Filtering AF
0.00335%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00303%
Overall
0.00349%
56/1,606,338 alleles · very rare
exomes 50/1,454,246 · genomes 6/152,092 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.00434% | 23,062 |
| Remaining individualsnot grpmax-eligible | 0.00322% | 31,089 |
| East Asian | 0.00228% | 43,828 |
| African / African-American | 0.00134% | 74,462 |
| South Asian | 0.00111% | 90,120 |
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.Ala528=
- Coding
- c.1584G>A
- MANE Select
- NM_020458
- dbSNP
- rs761294322
- Type
- single nucleotide variant
- Location
- chr2:47024302 (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.Ala528Val 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-ala528 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown