Is CEACAM6 p.Ala221Val (c.662C>T) pathogenic?

CEACAM6 p.Ala221Val (c.662C>T) is classified Likely benign in CEACAM6 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-11-29). AlphaMissense: likely benign (0.0641); Very rare (popmax 0.000847%, nfe).

How common is CEACAM6 p.Ala221Val (c.662C>T) in the general population?

CEACAM6 p.Ala221Val (c.662C>T) is very rare (popmax 0.000847%, nfe) (gnomAD).

What do computational predictors say about CEACAM6 p.Ala221Val (c.662C>T)?

AlphaMissense predicts likely benign (score 0.0641) — an in-silico prediction, not a clinical call.

CEACAM6 p.Ala221Val

c.662C>T · rs782220668 · VCV3141842

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0641 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000847%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0641	likely benign
REVEL	0.021	moderately benign-leaning
SaProt	LLR -3.13	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
Regional constraint	o/e 0.94	unconstrained · MANE · 11 kb · p 0.21 · regional, not allelic
Overall
CADD	0.482	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 0.000847% European (non-Finnish) · 10/1,180,030 alleles

Filtering AF 0.000429% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000312%

Overall 0.00062% 10/1,614,060 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: CEACAM6
Protein: p.Ala221Val
Coding: c.662C>T
MANE Select: NM_002483
dbSNP: rs782220668
Type: single nucleotide variant
Location: chr19:41761486 (GRCh38)
Gene constraint: LOEUF 0.908 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 88.52 · 6 PDB
Residue 221: the ig-like c2-type 1 domain

Full CEACAM6 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CEACAM6 p.Gly85Glu Benign ★★ same type
CEACAM6 p.His260= Benign ★★ same type
CEACAM6 p.Ala105Thr Uncertain significance ★ ⚠ same type
CEACAM6 p.Ala134Val Uncertain significance ★ ⚠ same type
CEACAM6 p.Arg225His Uncertain significance ★ ⚠ same type
CEACAM6 p.Arg250Cys Uncertain significance ★ ⚠ same type
CEACAM6 p.Arg250His Uncertain significance ★ ⚠ same type
CEACAM6 p.Arg340Met 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/ceacam6-p-ala221val (accessed [today's date]).

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