GUCY2C p.Phe752=
c.2256T>C · rs763353051 · VCV1088790
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 4 submitters
gnomAD v4.1
Rare
rare (popmax 0.171%, sas)
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 1.5 | GERP -1.9, phastCons 1 |
| Overall | ||
| CADD | 6.553 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.171%
South Asian · 155/90,902 alleles
Filtering AF
0.149%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.14%
Overall
0.0185%
297/1,607,406 alleles · rare
exomes 280/1,455,100 · genomes 17/152,306 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.171% | 586 |
| Middle Eastern | 0.116% | 864 |
| Ashkenazi Jewishnot grpmax-eligible | 0.0643% | 1,556 |
| Remaining individualsnot grpmax-eligible | 0.0161% | 6,220 |
| Admixed American | 0.015% | 6,663 |
| European (non-Finnish) | 0.00784% | 12,762 |
| Finnishnot grpmax-eligible | 0.00469% | 21,333 |
| African / African-American | 0.00267% | 37,463 |
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
- GUCY2C
- Protein
- p.Phe752=
- Coding
- c.2256T>C
- MANE Select
- NM_004963
- dbSNP
- rs763353051
- Type
- single nucleotide variant
- Location
- chr12:14625909 (GRCh38)
- Gene constraint
- LOEUF 1.118 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
- Structure
- AlphaFold pLDDT 80.08 · 3 PDB
Similar variants
- GUCY2C p.Asp387Gly Pathogenic ★★ ⚠ same type
- GUCY2C c.2602-1G>C Uncertain significance ★★ same type
- GUCY2C c.2776+5G>A Uncertain significance ★★ same type
- GUCY2C c.612-1G>A Uncertain significance ★★ same type
- GUCY2C p.Ala450Thr Uncertain significance ★★ ⚠ same type
- GUCY2C p.Ala48Gly Uncertain significance ★★ ⚠ same type
- GUCY2C p.Ala670Thr Uncertain significance ★★ ⚠ same type
- GUCY2C p.Ala897Thr 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/gucy2c-p-phe752 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown