Is CDH16 p.Arg772Cys (c.2314C>T) pathogenic?

CDH16 p.Arg772Cys (c.2314C>T) is classified Uncertain significance in CDH16 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-12-25). AlphaMissense: ambiguous (0.3474); Ultra-rare (popmax 0.0165%, sas).

How common is CDH16 p.Arg772Cys (c.2314C>T) in the general population?

CDH16 p.Arg772Cys (c.2314C>T) is ultra-rare (popmax 0.0165%, sas) (gnomAD).

What do computational predictors say about CDH16 p.Arg772Cys (c.2314C>T)?

AlphaMissense predicts ambiguous (score 0.3474) — an in-silico prediction, not a clinical call.

CDH16 p.Arg772Cys

c.2314C>T · VCV3830057

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3474 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0165%, sas)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.3474	ambiguous
REVEL	0.226	benign-leaning
SaProt	LLR -8.80	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 8.4	GERP 1.7, phastCons 1
Regional constraint	o/e 1.05	unconstrained · MANE · 9,670 bp · p 0.11 · regional, not allelic
Overall
CADD	27.7	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 0.0165% South Asian · 15/90,930 alleles

Filtering AF 0.0101% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00812%

Overall 0.00186% 27/1,449,094 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0165%	6,062
Remaining individualsnot grpmax-eligible	0.00486%	20,558
African / African-American	0.00134%	74,554
European (non-Finnish)	0.000682%	146,640

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: CDH16
Protein: p.Arg772Cys
Coding: c.2314C>T
MANE Select: NM_004062
Type: single nucleotide variant
Location: chr16:66909345 (GRCh38)
Gene constraint: LOEUF 1.079 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 82.17
Residue 772: the 'ectodomain g' region

Full CDH16 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CDH16 p.Arg772Ser Uncertain significance ★ ⚠ same residue
CDH16 p.Arg717His Benign ★★ same type
CDH16 p.Leu377= Benign ★★ same type
CDH16 p.Ala133Ser Uncertain significance ★ ⚠ same type
CDH16 p.Ala159Val Uncertain significance ★ ⚠ same type
CDH16 p.Ala173Thr Uncertain significance ★ ⚠ same type
CDH16 p.Ala202Val Uncertain significance ★ ⚠ same type
CDH16 p.Ala20Thr Uncertain significance ★ ⚠ 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/cdh16-p-arg772cys (accessed [today's date]).

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