Is CEACAM3 p.Pro42Ser (c.124C>T) pathogenic?

CEACAM3 p.Pro42Ser (c.124C>T) is classified Uncertain significance in CEACAM3 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-12-04). AlphaMissense: likely pathogenic (0.6512); Very rare (popmax 0.00534%, afr).

How common is CEACAM3 p.Pro42Ser (c.124C>T) in the general population?

CEACAM3 p.Pro42Ser (c.124C>T) is very rare (popmax 0.00534%, afr) (gnomAD).

What do computational predictors say about CEACAM3 p.Pro42Ser (c.124C>T)?

AlphaMissense predicts likely pathogenic (score 0.6512) — an in-silico prediction, not a clinical call.

CEACAM3 p.Pro42Ser

c.124C>T · VCV4651736

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6512 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00534%, afr)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.6512	likely pathogenic · top 7% in CEACAM3
REVEL	0.262	benign-leaning
SaProt	LLR -8.42	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 -0.44	GERP 1.7
Regional constraint	o/e 0.92	unconstrained · MANE · 15 kb · p 0.14 · regional, not allelic
Overall
CADD	14.45	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 0.00534% African / African-American · 4/74,906 alleles

Filtering AF 0.00175% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00104%

Overall 0.00263% 4/152,134 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: CEACAM3
Protein: p.Pro42Ser
Coding: c.124C>T
MANE Select: NM_001815
Type: single nucleotide variant
Location: chr19:41797648 (GRCh38)
Gene constraint: LOEUF 1.359 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 78.52 · 4 PDB
Residue 42: a β-strand; the ig-like v-type domain

Full CEACAM3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CEACAM3 p.Ala93Pro Benign ★★ same type
CEACAM3 p.Asn111= Likely benign ★★ same type
CEACAM3 p.Glu133Gly Benign ★★ ⚠ same type
CEACAM3 p.Leu78Gln Benign ★★ same type
CEACAM3 p.Ser77Arg Benign ★★ same type
CEACAM3 p.Thr103= Benign ★★ same type
CEACAM3 p.Thr135= Benign ★★ same type
CEACAM3 p.Tyr95Asn 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/ceacam3-p-pro42ser (accessed [today's date]).

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