TTC7A p.Phe648=
c.1944C>T · rs200604937 · VCV1156274
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0549%, sas)
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 -7.8 | GERP -4.8 |
| Overall | ||
| CADD | 7.759 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0549%
South Asian · 50/91,074 alleles
Filtering AF
0.0427%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0385%
Overall
0.013%
210/1,614,072 alleles · ultra-rare
exomes 202/1,461,780 · genomes 8/152,292 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.0549% | 1,821 |
| Remaining individualsnot grpmax-eligible | 0.0128% | 7,813 |
| European (non-Finnish) | 0.0128% | 7,814 |
| Ashkenazi Jewishnot grpmax-eligible | 0.00338% | 29,608 |
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.Phe648=
- Coding
- c.1944C>T
- MANE Select
- NM_020458
- dbSNP
- rs200604937
- Type
- single nucleotide variant
- Location
- chr2:47049973 (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 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
- TTC7A p.Gln526Ter 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-phe648 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown