Is CDH15 p.Arg571Cys (c.1711C>T) pathogenic?

CDH15 p.Arg571Cys (c.1711C>T) is classified Uncertain significance in CDH15 (ClinVar, Single submitter, 1 submitter; last evaluated 2017-10-05). AlphaMissense: ambiguous (0.4029); Absent from gnomAD v4.1.

How common is CDH15 p.Arg571Cys (c.1711C>T) in the general population?

CDH15 p.Arg571Cys (c.1711C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CDH15 p.Arg571Cys (c.1711C>T)?

AlphaMissense predicts ambiguous (score 0.4029) — an in-silico prediction, not a clinical call.

CDH15 p.Arg571Cys

c.1711C>T · rs1278544434 · VCV452625

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4029 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,533,118)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.4029	ambiguous
REVEL	0.288	benign-leaning
SaProt	LLR -9.64	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.9	GERP 0.56, phastCons 1
Regional constraint	o/e 1.18	unconstrained · MANE · 23 kb · p 5e-10 · regional, not allelic
Overall
CADD	25.3	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

No allele count reported in gnomAD v4.1 (AN 1,533,118). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: CDH15
Protein: p.Arg571Cys
Coding: c.1711C>T
MANE Select: NM_004933
dbSNP: rs1278544434
Type: single nucleotide variant
Location: chr16:89192300 (GRCh38)
Gene constraint: LOEUF 1.41 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 78.70
Residue 571: the cadherin 5 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-arg571cys (accessed [today's date]).

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