Is CEACAM6 p.Val331Ile (c.991G>A) pathogenic?

CEACAM6 p.Val331Ile (c.991G>A) is classified Uncertain significance in CEACAM6 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-03-31). AlphaMissense: likely benign (0.0976); Ultra-rare (popmax 0.0119%, amr).

How common is CEACAM6 p.Val331Ile (c.991G>A) in the general population?

CEACAM6 p.Val331Ile (c.991G>A) is ultra-rare (popmax 0.0119%, amr) (gnomAD).

What do computational predictors say about CEACAM6 p.Val331Ile (c.991G>A)?

AlphaMissense predicts likely benign (score 0.0976) — an in-silico prediction, not a clinical call.

CEACAM6 p.Val331Ile

c.991G>A · rs879945992 · VCV3141843

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0976 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0119%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0976	likely benign
REVEL	0.036	moderately benign-leaning
SaProt	LLR -7.84	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>C here scores Δ0.22 · evaluated, not missing
Constraint at this position
Conservation	phyloP 0.6
Regional constraint	o/e 0.94	unconstrained · MANE · 11 kb · p 0.21 · regional, not allelic
Overall
CADD	12.7	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 0.0119% Admixed American · 7/58,838 alleles

Filtering AF 0.00553% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00386%

Overall 0.00224% 36/1,607,076 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0119%	8,405
African / African-American	0.00805%	12,415
Remaining individualsnot grpmax-eligible	0.00643%	15,555
European (non-Finnish)	0.00161%	61,964

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.Val331Ile
Coding: c.991G>A
MANE Select: NM_002483
dbSNP: rs879945992
Type: single nucleotide variant
Location: chr19:41766215 (GRCh38)
Gene constraint: LOEUF 0.908 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 88.52 · 6 PDB

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-val331ile (accessed [today's date]).

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