C4A p.Phe1117=
c.3351C>T · rs777297715 · VCV2656434
Uncertain significance
Single submitter
Classification
Uncertain significance
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00224%, eas)
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 0.81 | GERP 1.4, phastCons 0.28 |
| Overall | ||
| CADD | 6.774 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00224%
East Asian · 1/44,722 alleles
Filtering AF
8.1e-05%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 5.5e-05%
Overall
0.000315%
5/1,587,542 alleles · very rare
exomes 5/1,437,964 · genomes 0/149,578 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.00224% | 44,722 |
| European (non-Finnish) | 0.000346% | 289,164 |
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
- C4A
- Protein
- p.Phe1117=
- Coding
- c.3351C>T
- MANE Select
- NM_007293
- dbSNP
- rs777297715
- Type
- single nucleotide variant
- Location
- chr6:31996075 (GRCh38)
- Gene constraint
- LOEUF 0.752 · pLI 0.11 (gnomAD)
- Structure
- AlphaFold pLDDT 83.56 · 12 PDB
Similar variants
- C4A c.2944+55T>C Benign/Likely benign ★★ same type
- C4A p.Asp1073Gly Benign/Likely benign ★★ same type
- C4A p.Pro1120Thr Likely benign ★★ same type
- C4B p.Ser1176Asn Benign ★★ same type
- C4B p.Thr907Ala Benign/Likely benign ★★ same type
- C4B c.3230+1G>A Likely pathogenic ★ same type
- C4B c.3676+1G>A Likely pathogenic ★ same type
- C4A p.Ala1062Val Uncertain significance ★ ⚠ 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/c4a-p-phe1117 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown