CEACAM5 p.Pro593=
c.1779G>A · rs147999822 · VCV778600
Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
low-frequency (popmax 4.55%, afr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.014 | strongly benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | <0.2 | all four deltas below 0.2 · G>T here scores Δ0.65 · evaluated, not missing |
| Constraint at this position | ||
| Conservation | phyloP -10 | GERP -3.4 |
| Overall | ||
| CADD | 5.494 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
4.55%
African / African-American · 3,405/74,900 alleles
Filtering AF
4.42%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 4.37%
Overall
0.251%
4,049/1,613,890 alleles · low-frequency
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 4.55% | 22 |
| Admixed American | 0.478% | 209 |
| Remaining individualsnot grpmax-eligible | 0.386% | 259 |
| Middle Eastern | 0.182% | 551 |
| South Asian | 0.0165% | 6,071 |
| European (non-Finnish) | 0.00746% | 13,409 |
| East Asian | 0.00446% | 22,426 |
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
- CEACAM5
- Protein
- p.Pro593=
- Coding
- c.1779G>A
- MANE Select
- NM_004363
- dbSNP
- rs147999822
- Type
- single nucleotide variant
- Location
- chr19:41720929 (GRCh38)
- Gene constraint
- LOEUF 1.007 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 87.44 · 6 PDB
- Residue 593
- the ig-like c2-type 6 domain; an α-helix
Similar variants
- CEACAM5 p.Ala301Val Benign ★★ ⚠ same type
- CEACAM5 p.Asp173= Benign ★★ same type
- CEACAM5 p.Asp588Asn Benign ★★ same type
- CEACAM5 p.Gly70= Benign ★★ same type
- CEACAM5 p.Ile100Thr Benign ★★ same type
- CEACAM5 p.Ile112Val Benign ★★ same type
- CEACAM5 p.Ile113Thr Benign ★★ same type
- CEACAM5 p.Ile80Val Benign ★★ 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/ceacam5-p-pro593 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown