Is CEACAM20 p.Pro196Ser (c.586C>T) pathogenic?

CEACAM20 p.Pro196Ser (c.586C>T) is classified Uncertain significance in CEACAM20 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-14). AlphaMissense: likely benign (0.0916); Very rare (popmax 0.000678%, nfe).

How common is CEACAM20 p.Pro196Ser (c.586C>T) in the general population?

CEACAM20 p.Pro196Ser (c.586C>T) is very rare (popmax 0.000678%, nfe) (gnomAD).

What do computational predictors say about CEACAM20 p.Pro196Ser (c.586C>T)?

AlphaMissense predicts likely benign (score 0.0916) — an in-silico prediction, not a clinical call.

CEACAM20 p.Pro196Ser

c.586C>T · VCV4224962

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0916 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000678%, nfe)

Missense predictors

0/2 damaging

AlphaMissense, SaProt

Computational evidence

Protein change
AlphaMissense	0.0916	likely benign
SaProt	LLR -7.92	tolerated
⇒ AlphaMissense and SaProt both call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -4.5	GERP -2
Regional constraint	o/e 0.93	unconstrained · MANE · 23 kb · p 0.049 · regional, not allelic
Overall
CADD	0.073	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000678% European (non-Finnish) · 8/1,179,830 alleles

Filtering AF 0.000292% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000211%

Overall 0.000496% 8/1,613,626 alleles · very rare

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: CEACAM20
Protein: p.Pro196Ser
Coding: c.586C>T
MANE Select: NM_001102597
Type: single nucleotide variant
Location: chr19:44522799 (GRCh38)
Gene constraint: LOEUF 1.054 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 73.87
Residue 196: the ig-like c2-type 2 domain

Full CEACAM20 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CEACAM20 p.Ala143Thr Uncertain significance ★ ⚠ same type
CEACAM20 p.Ala426Val Uncertain significance ★ ⚠ same type
CEACAM20 p.Ala4Thr Uncertain significance ★ ⚠ same type
CEACAM20 p.Arg113Cys Uncertain significance ★ ⚠ same type
CEACAM20 p.Arg148Lys Uncertain significance ★ ⚠ same type
CEACAM20 p.Arg316Gln Uncertain significance ★ ⚠ same type
CEACAM20 p.Arg334Trp Uncertain significance ★ ⚠ same type
CEACAM20 p.Arg353Lys 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/ceacam20-p-pro196ser (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown