Is CDH15 p.Asn107Ser (c.320A>G) pathogenic?

CDH15 p.Asn107Ser (c.320A>G) is classified Uncertain significance in CDH15 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-04-23). AlphaMissense: likely benign (0.1668); Ultra-rare (popmax 0.096%, afr).

How common is CDH15 p.Asn107Ser (c.320A>G) in the general population?

CDH15 p.Asn107Ser (c.320A>G) is ultra-rare (popmax 0.096%, afr) (gnomAD).

What do computational predictors say about CDH15 p.Asn107Ser (c.320A>G)?

AlphaMissense predicts likely benign (score 0.1668) — an in-silico prediction, not a clinical call.

CDH15 p.Asn107Ser

c.320A>G · VCV3265181

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1668 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.096%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1668	likely benign
REVEL	0.127	moderately benign-leaning
SaProt	LLR -9.83	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 11	GERP 1.7, phastCons 1
Regional constraint	o/e 1.18	unconstrained · MANE · 23 kb · p 5e-10 · regional, not allelic
Overall
CADD	21.4	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 0.096% African / African-American · 72/75,032 alleles

Filtering AF 0.0781% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0716%

Overall 0.00595% 96/1,612,766 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.096%	1,042
Admixed American	0.00667%	14,986
Remaining individualsnot grpmax-eligible	0.0048%	20,820
European (non-Finnish)	0.00144%	69,391

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.Asn107Ser
Coding: c.320A>G
MANE Select: NM_004933
Type: single nucleotide variant
Location: chr16:89180318 (GRCh38)
Gene constraint: LOEUF 1.41 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 78.70
Residue 107: the cadherin 1 domain

Full CDH15 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/cdh15-p-asn107ser (accessed [today's date]).

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