Is CEACAM4 p.Ala80Val (c.239C>T) pathogenic?

CEACAM4 p.Ala80Val (c.239C>T) is classified Uncertain significance in CEACAM4 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-25). AlphaMissense: likely benign (0.1448); Ultra-rare (popmax 0.0227%, afr).

How common is CEACAM4 p.Ala80Val (c.239C>T) in the general population?

CEACAM4 p.Ala80Val (c.239C>T) is ultra-rare (popmax 0.0227%, afr) (gnomAD).

What do computational predictors say about CEACAM4 p.Ala80Val (c.239C>T)?

AlphaMissense predicts likely benign (score 0.1448) — an in-silico prediction, not a clinical call.

CEACAM4 p.Ala80Val

c.239C>T · VCV4224985

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1448 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0227%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1448	likely benign
REVEL	0.052	moderately benign-leaning
SaProt	LLR -7.59	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 1.07	unconstrained · MANE · 7,630 bp · p 0.21 · regional, not allelic
Overall
CADD	0.07	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0227% African / African-American · 17/74,988 alleles

Filtering AF 0.0144% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0118%

Overall 0.00124% 20/1,613,984 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0227%	4,411
Remaining individualsnot grpmax-eligible	0.0032%	31,253
South Asian	0.0011%	91,084

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: CEACAM4
Protein: p.Ala80Val
Coding: c.239C>T
MANE Select: NM_001817
Type: single nucleotide variant
Location: chr19:41625786 (GRCh38)
Gene constraint: LOEUF 1.452 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 76.99
Residue 80: the ig-like v-type domain

Full CEACAM4 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CEACAM4 p.Ala127Thr Uncertain significance ★ ⚠ same type
CEACAM4 p.Ala182Ser Uncertain significance ★ ⚠ same type
CEACAM4 p.Arg98Gln Uncertain significance ★ ⚠ same type
CEACAM4 p.Arg9Cys Uncertain significance ★ ⚠ same type
CEACAM4 p.Asn111Asp Uncertain significance ★ ⚠ same type
CEACAM4 p.Asp116Gly Uncertain significance ★ ⚠ same type
CEACAM4 p.Asp130Asn Uncertain significance ★ ⚠ same type
CEACAM4 p.Asp132Asn 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/ceacam4-p-ala80val (accessed [today's date]).

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