Is CEACAM5 p.Pro103Ser (c.307C>T) pathogenic?

CEACAM5 p.Pro103Ser (c.307C>T) is classified Benign in CEACAM5 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2018-05-08). AlphaMissense: likely benign (0.0817); Low-frequency (popmax 1.63%, afr).

How common is CEACAM5 p.Pro103Ser (c.307C>T) in the general population?

CEACAM5 p.Pro103Ser (c.307C>T) is low-frequency (popmax 1.63%, afr) (gnomAD).

What do computational predictors say about CEACAM5 p.Pro103Ser (c.307C>T)?

AlphaMissense predicts likely benign (score 0.0817) — an in-silico prediction, not a clinical call.

CEACAM5 p.Pro103Ser

c.307C>T · rs74626868 · VCV775412

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0817 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 1.63%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0817	likely benign
REVEL	0.035	moderately benign-leaning
SaProt	LLR -4.45	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -20	GERP -3.4
Regional constraint	o/e 0.91	unconstrained · MANE · 19 kb · p 0.011 · regional, not allelic
Overall
CADD	0.029	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 1.63% African / African-American · 1,221/74,964 alleles

Filtering AF 1.55% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.52%

Overall 0.0895% 1,445/1,614,004 alleles · low-frequency

Ancestry group	Frequency	1 in
African / African-Americangrpmax	1.63%	61
Middle Eastern	0.181%	551
Remaining individualsnot grpmax-eligible	0.163%	613
Admixed American	0.122%	822
South Asian	0.0176%	5,692
Ashkenazi Jewishnot grpmax-eligible	0.00676%	14,801
European (non-Finnish)	0.00161%	62,104
Finnishnot grpmax-eligible	0.00156%	64,024

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.Pro103Ser
Coding: c.307C>T
MANE Select: NM_004363
dbSNP: rs74626868
Type: single nucleotide variant
Location: chr19:41709922 (GRCh38)
Gene constraint: LOEUF 1.007 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 87.44 · 6 PDB
Residue 103: the ig-like v-type domain; a turn

Full CEACAM5 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

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-pro103ser (accessed [today's date]).

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