Is CEACAM1 p.Ser154Phe (c.461C>T) pathogenic?

CEACAM1 p.Ser154Phe (c.461C>T) is classified Uncertain significance in CEACAM1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-10-22). AlphaMissense: likely benign (0.129); Absent from gnomAD v4.1.

How common is CEACAM1 p.Ser154Phe (c.461C>T) in the general population?

CEACAM1 p.Ser154Phe (c.461C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CEACAM1 p.Ser154Phe (c.461C>T)?

AlphaMissense predicts likely benign (score 0.129) — an in-silico prediction, not a clinical call.

CEACAM1 p.Ser154Phe

c.461C>T · VCV4651721

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.129 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.129	likely benign
REVEL	0.084	moderately benign-leaning
SaProt	LLR -10.12	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.1	GERP -0.5
Regional constraint	o/e 0.88	unconstrained · MANE · 19 kb · p 0.003 · regional, not allelic
Overall
CADD	19.16	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: CEACAM1
Protein: p.Ser154Phe
Coding: c.461C>T
MANE Select: NM_001712
Type: single nucleotide variant
Location: chr19:42522166 (GRCh38)
Gene constraint: LOEUF 0.826 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.51 · 19 PDB
Residue 154: the ig-like c2-type 1 domain

Full CEACAM1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CEACAM1 p.Asn111= Likely benign ★★ same type
CEACAM1 p.Leu53= Likely benign ★★ same type
CEACAM1 p.Ala6Val Uncertain significance ★ ⚠ same type
CEACAM1 p.Ala83Thr Uncertain significance ★ ⚠ same type
CEACAM1 p.Arg98Gln Uncertain significance ★ ⚠ same type
CEACAM1 p.Asn274Asp Uncertain significance ★ ⚠ same type
CEACAM1 p.Asn351Ser Uncertain significance ★ ⚠ same type
CEACAM1 p.Asn400Ser 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/ceacam1-p-ser154phe (accessed [today's date]).

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