Is CEACAM3 p.Ser77Arg (c.229A>C) pathogenic?

CEACAM3 p.Ser77Arg (c.229A>C) is classified Benign in CEACAM3 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2018-07-23). AlphaMissense: likely benign (0.0794); Common (popmax 15.2%, afr) — too common for a highly-penetrant pathogenic allele.

What do computational predictors say about CEACAM3 p.Ser77Arg (c.229A>C)?

AlphaMissense predicts likely benign (score 0.0794) — an in-silico prediction, not a clinical call.

CEACAM3 p.Ser77Arg

Q: How common is CEACAM3 p.Ser77Arg (c.229A>C) in the general population?

CEACAM3 p.Ser77Arg (c.229A>C) is common (popmax 15.2%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.229A>C · rs61738270 · VCV769003

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0794 · ACMG-weighted

gnomAD v4.1

Common

common (popmax 15.2%, afr) — too common for a highly-penetrant pathogenic allele

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0794	likely benign
REVEL	0.044	moderately benign-leaning
SaProt	LLR -4.44	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 0.92	unconstrained · MANE · 15 kb · p 0.14 · regional, not allelic
Overall
CADD	0.005	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 15.2% African / African-American · 10,477/69,050 alleles

Filtering AF 14.9% ClinGen BA1/BS1 input FAF95, joint · FAF99 14.8%

Overall 0.807% 12,966/1,605,928 alleles · common

Ancestry group	Frequency	1 in
African / African-Americangrpmax	15.2%	7
Ashkenazi Jewishnot grpmax-eligible	2.56%	39
Remaining individualsnot grpmax-eligible	1.17%	86
Admixed American	0.957%	105
Middle Eastern	0.613%	163
South Asian	0.0472%	2,117
European (non-Finnish)	0.0319%	3,137

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.Ser77Arg
Coding: c.229A>C
MANE Select: NM_001815
dbSNP: rs61738270
Type: single nucleotide variant
Location: chr19:41797753 (GRCh38)
Gene constraint: LOEUF 1.359 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 78.52 · 4 PDB
Residue 77: an α-helix; 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.Thr103= Benign ★★ same type
CEACAM3 p.Thr135= Benign ★★ same type
CEACAM3 p.Tyr95Asn Benign ★★ same type
CEACAM3 p.Val83Ala 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-ser77arg (accessed [today's date]).

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