Is CDH15 p.Arg36Gln (c.107G>A) pathogenic?

CDH15 p.Arg36Gln (c.107G>A) is classified Conflicting classifications of pathogenicity in CDH15 (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2023-03-27). AlphaMissense: likely benign (0.076); Ultra-rare (popmax 0.0692%, sas); Associated with CDH15-related disorder.

What condition is associated with CDH15 p.Arg36Gln (c.107G>A)?

CDH15 p.Arg36Gln (c.107G>A) is associated with CDH15-related disorder (ClinVar).

How common is CDH15 p.Arg36Gln (c.107G>A) in the general population?

CDH15 p.Arg36Gln (c.107G>A) is ultra-rare (popmax 0.0692%, sas) (gnomAD).

What do computational predictors say about CDH15 p.Arg36Gln (c.107G>A)?

AlphaMissense predicts likely benign (score 0.076) — an in-silico prediction, not a clinical call.

CDH15 p.Arg36Gln

c.107G>A · rs367770505 · VCV210623

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.076 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0692%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

CDH15-related disorder

Computational evidence

Protein change
AlphaMissense	0.076	likely benign
REVEL	0.031	moderately benign-leaning
SaProt	LLR -7.04	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 -1.5	GERP -2.5
Regional constraint	o/e 1.18	unconstrained · MANE · 23 kb · p 5e-10 · regional, not allelic
Overall
CADD	2.778	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0692% South Asian · 63/91,086 alleles

Filtering AF 0.0554% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0505%

Overall 0.00744% 120/1,613,518 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0692%	1,446
African / African-American	0.0386%	2,588
Middle Eastern	0.0165%	6,058
Remaining individualsnot grpmax-eligible	0.0112%	8,927
East Asian	0.00446%	22,438
Admixed American	0.00167%	60,020
European (non-Finnish)	0.00144%	69,406

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.Arg36Gln
Coding: c.107G>A
MANE Select: NM_004933
dbSNP: rs367770505
Type: single nucleotide variant
Location: chr16:89179480 (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

Disease context

CDH15-related disorder

Similar variants

CDH3 p.Val36= Likely benign ★ same residue
CDH3 c.1796-2A>G Pathogenic ★★ same condition
CDH3 p.Arg103Ter Pathogenic ★★ same condition
CDH3 p.Arg503His Pathogenic/Likely pathogenic ★★ ⚠ same condition
CDH3 p.Val205Met Likely pathogenic ★★ same condition
CDH3 p.Met269Thr Uncertain significance ★★ ⚠ same condition
CDH3 p.Glu289Ter Likely pathogenic ★ same condition
CDH15 p.Ala174Ser Uncertain significance ★ ⚠ 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/cdh15-p-arg36gln (accessed [today's date]).

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