Is CDH1 p.Ser838= (c.2514C>T) pathogenic?

CDH1 p.Ser838= (c.2514C>T) is classified Benign/Likely benign in CDH1 (ClinVar, Multiple submitters, 10 submitters; last evaluated 2025-10-29). Very rare (popmax 0.00666%, afr); Associated with ovarian cancer.

What condition is associated with CDH1 p.Ser838= (c.2514C>T)?

CDH1 p.Ser838= (c.2514C>T) is associated with ovarian cancer, hereditary diffuse gastric adenocarcinoma, hereditary neoplastic syndrome (ClinVar).

How common is CDH1 p.Ser838= (c.2514C>T) in the general population?

CDH1 p.Ser838= (c.2514C>T) is very rare (popmax 0.00666%, afr) (gnomAD).

CDH1 p.Ser838=

c.2514C>T · rs770974998 · VCV184105

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 10 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00666%, afr)

Conditions

ovarian cancer

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -9.6	GERP -3.9
Overall
CADD	2.834	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00666% African / African-American · 5/75,046 alleles

Filtering AF 0.00255% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00161%

Overall 0.00137% 20/1,461,856 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00666%	15,009
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,604
European (non-Finnish)	0.00119%	84,286

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: CDH1
Protein: p.Ser838=
Coding: c.2514C>T
MANE Select: NM_004360
dbSNP: rs770974998
Type: single nucleotide variant
Location: chr16:68833364 (GRCh38)
Gene constraint: LOEUF 0.514 · pLI 0.86 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 79.13 · 22 PDB
Residue 838: the 'required for binding alpha, beta and gamma catenins' region; a modified residue (phosphoserine); a UniProt-annotated variant site (in an ovarian carcinoma sample; somatic mutation; loss of heterozygosity)

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

Disease context

ovarian cancer — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: hereditary diffuse gastric adenocarcinoma hereditary neoplastic syndrome hereditary breast carcinoma

Similar variants

CDH1 p.Ser838Gly Likely benign ★★★ same residue
CDH1 p.Ser838Asn Uncertain significance ★★ ⚠ same residue
CDH1 p.Ser838Arg Uncertain significance ★ ⚠ same residue
CDH1 p.Ser838Ile Uncertain significance ★ ⚠ same residue
CDH1 c.1008+2T>C Likely pathogenic ★★★ same condition
CDH1 c.1137+1G>A Pathogenic ★★★ same condition
CDH1 c.1137+2T>C Likely pathogenic ★★★ same condition
CDH1 c.1320+1G>C Likely 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-ser838 (accessed [today's date]).

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