Is CDH1 p.Gln16Lys (c.46C>A) pathogenic?

CDH1 p.Gln16Lys (c.46C>A) is classified Conflicting classifications of pathogenicity in CDH1 (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2024-12-24). AlphaMissense: likely benign (0.2132); Absent from gnomAD v4.1; Associated with hereditary neoplastic syndrome.

What condition is associated with CDH1 p.Gln16Lys (c.46C>A)?

CDH1 p.Gln16Lys (c.46C>A) is associated with hereditary neoplastic syndrome (ClinVar).

How common is CDH1 p.Gln16Lys (c.46C>A) in the general population?

CDH1 p.Gln16Lys (c.46C>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CDH1 p.Gln16Lys (c.46C>A)?

AlphaMissense predicts likely benign (score 0.2132) — an in-silico prediction, not a clinical call.

CDH1 p.Gln16Lys

c.46C>A · rs770244203 · VCV1692799

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.2132 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,537,412)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

hereditary neoplastic syndrome

Computational evidence

Protein change
AlphaMissense	0.2132	likely benign
REVEL	0.222	benign-leaning
SaProt	LLR -8.84	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>T here scores Δ0.96 · evaluated, not missing
Constraint at this position
Conservation	phyloP 4.5	GERP 2.2, phastCons 1
Regional constraint	o/e 1.05	unconstrained · MANE · 71 kb · p 0.52 · regional, not allelic
Overall
CADD	21.6	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

No allele count reported in gnomAD v4.1 (AN 1,537,412). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: CDH1
Protein: p.Gln16Lys
Coding: c.46C>A
MANE Select: NM_004360
dbSNP: rs770244203
Type: single nucleotide variant
Location: chr16:68737461 (GRCh38)
Gene constraint: LOEUF 0.514 · pLI 0.86 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 79.13 · 22 PDB

Full CDH1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

hereditary neoplastic syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CDH1 p.Gln16Arg Uncertain significance ★★ ⚠ same residue
CDH1 p.Gln16Leu Uncertain significance ★★ ⚠ same residue
CDH1 p.Gln16= Conflicting classifications of pathogenicity ★ same residue
CDH1 p.Gln16His Conflicting classifications of pathogenicity ★ ⚠ same residue
CDH1 p.Gln16Ter Pathogenic ★★ same residue
CDH1 p.Gln16Glu Uncertain significance ★ ⚠ same residue
CDH1 c.1008+2T>C Likely pathogenic ★★★ same condition
CDH1 c.1137+1G>A Pathogenic ★★★ 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/cdh1-p-gln16lys (accessed [today's date]).

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