Is CEACAM16 p.Leu26Val (c.76C>G) pathogenic?

CEACAM16 p.Leu26Val (c.76C>G) is classified Uncertain significance in CEACAM16 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-07-22). AlphaMissense: likely benign (0.0597); Ultra-rare (popmax 0.01%, amr).

How common is CEACAM16 p.Leu26Val (c.76C>G) in the general population?

CEACAM16 p.Leu26Val (c.76C>G) is ultra-rare (popmax 0.01%, amr) (gnomAD).

What do computational predictors say about CEACAM16 p.Leu26Val (c.76C>G)?

AlphaMissense predicts likely benign (score 0.0597) — an in-silico prediction, not a clinical call.

CEACAM16 p.Leu26Val

c.76C>G · rs778614897 · VCV1509130

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0597 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.01%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0597	likely benign
REVEL	0.075	moderately benign-leaning
SaProt	LLR -6.14	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 4.6	GERP 0.99, phastCons 1
Regional constraint	o/e 0.89	unconstrained · MANE · 9,046 bp · p 0.0079 · regional, not allelic
Overall
CADD	15.52	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 0.01% Admixed American · 6/60,000 alleles

Filtering AF 0.00428% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00295%

Overall 0.000372% 6/1,613,500 alleles · ultra-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: CEACAM16
Protein: p.Leu26Val
Coding: c.76C>G
MANE Select: NM_001039213
dbSNP: rs778614897
Type: single nucleotide variant
Location: chr19:44703387 (GRCh38)
Gene constraint: LOEUF 1.139 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 90.50

Full CEACAM16 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CEACAM16 c.1267+1G>A Uncertain significance ★★ same type
CEACAM16 p.Ala198Thr Uncertain significance ★★ ⚠ same type
CEACAM16 p.Ala355Thr Uncertain significance ★★ ⚠ same type
CEACAM16 p.Ala372Thr Uncertain significance ★★ ⚠ same type
CEACAM16 p.Ala375Val Uncertain significance ★★ ⚠ same type
CEACAM16 p.Ala50Thr Uncertain significance ★★ ⚠ same type
CEACAM16 p.Arg145Cys Uncertain significance ★★ ⚠ same type
CEACAM16 p.Arg150His 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/ceacam16-p-leu26val (accessed [today's date]).

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