Is CEACAM16 p.Pro366Arg (c.1097C>G) pathogenic?

CEACAM16 p.Pro366Arg (c.1097C>G) is classified Uncertain significance in CEACAM16 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-08-26). AlphaMissense: likely pathogenic (0.6613); Very rare (popmax 8.48e-05%, nfe).

How common is CEACAM16 p.Pro366Arg (c.1097C>G) in the general population?

CEACAM16 p.Pro366Arg (c.1097C>G) is very rare (popmax 8.48e-05%, nfe) (gnomAD).

What do computational predictors say about CEACAM16 p.Pro366Arg (c.1097C>G)?

AlphaMissense predicts likely pathogenic (score 0.6613) — an in-silico prediction, not a clinical call.

CEACAM16 p.Pro366Arg

c.1097C>G · rs762367899 · VCV1445916

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6613 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.48e-05%, nfe)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.6613	likely pathogenic
REVEL	0.265	benign-leaning
SaProt	LLR -7.84	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.8	GERP 1.6, phastCons 1
Regional constraint	o/e 0.89	unconstrained · MANE · 9,046 bp · p 0.0079 · regional, not allelic
Overall
CADD	25.6	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.48e-05% European (non-Finnish) · 1/1,179,116 alleles

Overall 6.85e-05% 1/1,459,000 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: CEACAM16
Protein: p.Pro366Arg
Coding: c.1097C>G
MANE Select: NM_001039213
dbSNP: rs762367899
Type: single nucleotide variant
Location: chr19:44708017 (GRCh38)
Gene constraint: LOEUF 1.139 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 90.50

Full CEACAM16 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CEACAM16 p.Pro366Leu Conflicting classifications of pathogenicity ★ ⚠ same residue
CEACAM16 p.Pro366= Likely benign ★ same residue
CEACAM16 c.1267+1G>A Uncertain significance ★★ same type
CEACAM16 p.Ala198Thr Uncertain significance ★★ ⚠ same type
CEACAM16 p.Ala355Thr Uncertain significance ★★ ⚠ same type
CEACAM16 p.Ala372Thr Uncertain significance ★★ ⚠ same type
CEACAM16 p.Ala375Val Uncertain significance ★★ ⚠ same type
CEACAM16 p.Ala50Thr 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/ceacam16-p-pro366arg (accessed [today's date]).

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