FECH c.1077+252T>C
Benign
Single submitter
Classification
Benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Common
common (popmax 31.9%, eas) — too common for a highly-penetrant pathogenic allele
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| Splice region | donor +252 | deep intronic (+252 nt into the intron) |
|---|---|---|
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 0.003 | GERP -1.1 |
| Non-coding constraint | Z 2.27 | 1 kb window · o/e 0.78 · regional · uncalibrated |
| Overall | ||
| CADD | 3.255 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
31.9%
East Asian · 1,652/5,178 alleles
Filtering AF
30.6%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 30.1%
Overall
8.74%
13,305/152,288 alleles · common
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 31.9% | 3 |
| Admixed American | 23% | 4 |
| Remaining individualsnot grpmax-eligible | 11.2% | 9 |
| South Asian | 10.4% | 10 |
| European (non-Finnish) | 7.8% | 13 |
| Finnishnot grpmax-eligible | 6.86% | 15 |
| Ashkenazi Jewishnot grpmax-eligible | 6.62% | 15 |
| Middle Eastern | 5.78% | 17 |
| African / African-American | 2.68% | 37 |
| Amishnot grpmax-eligible | 0.33% | 303 |
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
- FECH
- Coding
- c.1077+252T>C
- MANE Select
- NM_000140
- dbSNP
- rs72627248
- Type
- single nucleotide variant
- Location
- chr18:57554008 (GRCh38)
- Gene constraint
- LOEUF 0.859 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 87.37 · 25 PDB
Similar variants
- FECH c.1137+3A>G Pathogenic/Likely pathogenic ★★ same type
- FECH c.314+2T>G Pathogenic/Likely pathogenic ★★ same type
- FECH c.463+1G>C Pathogenic ★★ same type
- FECH c.598+1G>T Pathogenic ★★ same type
- FECH c.599-2A>G Pathogenic ★★ same type
- FECH c.913-2A>G Likely pathogenic ★★ same type
- FECH p.Arg115Ter Pathogenic/Likely pathogenic ★★ same type
- FECH p.Arg298Ter 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/fech-c-1077-plus-252t-c (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown