Is CDH3 p.Ser308Phe (c.923C>T) pathogenic?

CDH3 p.Ser308Phe (c.923C>T) is classified Uncertain significance in CDH3 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-04-09). AlphaMissense: likely benign (0.1317); Very rare (popmax 0.00161%, nfe).

How common is CDH3 p.Ser308Phe (c.923C>T) in the general population?

CDH3 p.Ser308Phe (c.923C>T) is very rare (popmax 0.00161%, nfe) (gnomAD).

What do computational predictors say about CDH3 p.Ser308Phe (c.923C>T)?

AlphaMissense predicts likely benign (score 0.1317) — an in-silico prediction, not a clinical call.

CDH3 p.Ser308Phe

c.923C>T · rs770630272 · VCV1948117

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1317 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00161%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1317	likely benign
REVEL	0.081	moderately benign-leaning
SaProt	LLR 0.04	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 2.2	GERP 1.1, phastCons 0.98
Regional constraint	o/e 0.97	unconstrained · MANE · 53 kb · p 0.35 · 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 0.00161% European (non-Finnish) · 19/1,180,004 alleles

Filtering AF 0.00103% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00083%

Overall 0.00118% 19/1,614,104 alleles · very rare exomes 19/1,461,836 · genomes 0/152,268 · joint denominator

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: CDH3
Protein: p.Ser308Phe
Coding: c.923C>T
MANE Select: NM_001793
dbSNP: rs770630272
Type: single nucleotide variant
Location: chr16:68681023 (GRCh38)
Gene constraint: LOEUF 0.823 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 76.71 · 19 PDB
Residue 308: the cadherin 2 domain

Full CDH3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CDH3 c.1796-2A>G Pathogenic ★★ same type
CDH3 c.691+1G>A Pathogenic/Likely pathogenic ★★ same type
CDH3 p.Arg103Ter Pathogenic ★★ same type
CDH3 p.Arg221Ter Pathogenic ★★ same type
CDH3 p.Arg503His Pathogenic/Likely pathogenic ★★ ⚠ same type
CDH3 p.Gln299Ter Pathogenic ★★ same type
CDH3 p.Glu708Ter Likely pathogenic ★★ same type
CDH3 p.Trp362Ter Pathogenic ★★ 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/cdh3-p-ser308phe (accessed [today's date]).

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