Is CEACAM16 p.Val317Phe (c.949G>T) pathogenic?

CEACAM16 p.Val317Phe (c.949G>T) is classified Uncertain significance in CEACAM16 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-05-23). AlphaMissense: likely benign (0.1003); Ultra-rare (popmax 0.0115%, eas); Associated with Inborn genetic diseases.

What condition is associated with CEACAM16 p.Val317Phe (c.949G>T)?

CEACAM16 p.Val317Phe (c.949G>T) is associated with Inborn genetic diseases (ClinVar).

How common is CEACAM16 p.Val317Phe (c.949G>T) in the general population?

CEACAM16 p.Val317Phe (c.949G>T) is ultra-rare (popmax 0.0115%, eas) (gnomAD).

What do computational predictors say about CEACAM16 p.Val317Phe (c.949G>T)?

AlphaMissense predicts likely benign (score 0.1003) — an in-silico prediction, not a clinical call.

CEACAM16 p.Val317Phe

c.949G>T · VCV3999905

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1003 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0115%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1003	likely benign
REVEL	0.112	moderately benign-leaning
SaProt	LLR -8.74	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 3	GERP 1.5, phastCons 0.97
Regional constraint	o/e 0.89	unconstrained · MANE · 9,046 bp · p 0.0079 · regional, not allelic
Overall
CADD	20.5	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 0.0115% East Asian · 5/43,416 alleles

Filtering AF 0.00447% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00294%

Overall 0.000324% 5/1,543,350 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.Val317Phe
Coding: c.949G>T
MANE Select: NM_001039213
Type: single nucleotide variant
Location: chr19:44707869 (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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CEACAM16 p.Ala355Thr Uncertain significance ★★ ⚠ same condition
CEACAM16 p.Ala372Thr Uncertain significance ★★ ⚠ same condition
CEACAM16 p.Ala375Val Uncertain significance ★★ ⚠ same condition
CEACAM16 p.Ala50Thr Uncertain significance ★★ ⚠ same condition
CEACAM16 p.Arg145Cys Uncertain significance ★★ ⚠ same condition
CEACAM16 p.Arg193Trp Uncertain significance ★★ ⚠ same condition
CEACAM16 p.Arg225Cys Uncertain significance ★★ ⚠ same condition
CEACAM16 p.Arg225His Uncertain significance ★★ ⚠ same condition

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-val317phe (accessed [today's date]).

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