Is CDH3 p.Val734Met (c.2200G>A) pathogenic?

CDH3 p.Val734Met (c.2200G>A) is classified Uncertain significance in CDH3 (ClinVar, Single submitter, 2 submitters; last evaluated 2022-06-04). AlphaMissense: likely benign (0.1812); Ultra-rare (popmax 0.0657%, mid); Associated with retinitis pigmentosa.

What condition is associated with CDH3 p.Val734Met (c.2200G>A)?

CDH3 p.Val734Met (c.2200G>A) is associated with retinitis pigmentosa (ClinVar).

How common is CDH3 p.Val734Met (c.2200G>A) in the general population?

CDH3 p.Val734Met (c.2200G>A) is ultra-rare (popmax 0.0657%, mid) (gnomAD).

How is Retinitis pigmentosa inherited?

Typically Autosomal dominant, Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

What do computational predictors say about CDH3 p.Val734Met (c.2200G>A)?

AlphaMissense predicts likely benign (score 0.1812) — an in-silico prediction, not a clinical call.

CDH3 p.Val734Met

c.2200G>A · rs775541873 · VCV812257

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1812 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0657%, mid)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

retinitis pigmentosa

Computational evidence

Protein change
AlphaMissense	0.1812	likely benign
REVEL	0.531	indeterminate
SaProt	LLR -7.46	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2.1, phastCons 1
Overall
CADD	28.5	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 0.0657% Middle Eastern · 4/6,084 alleles

Filtering AF 0.0224% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0135%

Overall 0.00118% 19/1,613,932 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0657%	1,521
South Asian	0.0022%	45,537
Admixed American	0.00167%	59,992
European (non-Finnish)	0.00102%	98,334

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.Val734Met
Coding: c.2200G>A
MANE Select: NM_004933 · reported on NM_001793
dbSNP: rs775541873
Type: single nucleotide variant
Location: chr16:68695843 (GRCh38)
Structure: AlphaFold pLDDT 78.70

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

Disease context

retinitis pigmentosa — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Retinitis pigmentosa (Orphanet):

Inheritance: Autosomal dominant, Autosomal recessive, Mitochondrial inheritance
Onset: Adolescent, Adult, Childhood
Prevalence: 1-5 / 10 000 (Europe)

Similar variants

CDH3 p.Met1Ile Likely pathogenic same condition
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

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-val734met (accessed [today's date]).

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