Is CDH15 p.Arg42= (c.126C>T) pathogenic?

CDH15 p.Arg42= (c.126C>T) is classified Likely benign in CDH15 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-05-06). Ultra-rare (popmax 0.0799%, afr).

How common is CDH15 p.Arg42= (c.126C>T) in the general population?

CDH15 p.Arg42= (c.126C>T) is ultra-rare (popmax 0.0799%, afr) (gnomAD).

CDH15 p.Arg42=

c.126C>T · VCV4931993

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0799%, afr)

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 -8.2	GERP -2.5
Overall
CADD	0.173	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0799% African / African-American · 60/75,054 alleles

Filtering AF 0.0637% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0579%

Overall 0.00812% 131/1,613,298 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0799%	1,251
Admixed American	0.0267%	3,750
South Asian	0.0253%	3,959
Middle Eastern	0.0165%	6,054
Remaining individualsnot grpmax-eligible	0.0144%	6,942
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,576
European (non-Finnish)	0.00178%	56,181

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: CDH15
Protein: p.Arg42=
Coding: c.126C>T
MANE Select: NM_004933
Type: single nucleotide variant
Location: chr16:89179499 (GRCh38)
Gene constraint: LOEUF 1.41 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 78.70

Full CDH15 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CDH15 p.Arg42Cys Uncertain significance ★ ⚠ same residue
CDH15 p.Arg42Leu Uncertain significance ★ ⚠ same residue
CDH3 p.Gly42Asp Uncertain significance ★ ⚠ same residue
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

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/cdh15-p-arg42 (accessed [today's date]).

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