Is CDH16 p.Arg772Ser (c.2314C>A) pathogenic?

CDH16 p.Arg772Ser (c.2314C>A) is classified Uncertain significance in CDH16 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-11-02). AlphaMissense: ambiguous (0.4738); Ultra-rare (popmax 0.0682%, sas).

How common is CDH16 p.Arg772Ser (c.2314C>A) in the general population?

CDH16 p.Arg772Ser (c.2314C>A) is ultra-rare (popmax 0.0682%, sas) (gnomAD).

What do computational predictors say about CDH16 p.Arg772Ser (c.2314C>A)?

AlphaMissense predicts ambiguous (score 0.4738) — an in-silico prediction, not a clinical call.

CDH16 p.Arg772Ser

c.2314C>A · rs781254169 · VCV3141140

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4738 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0682%, sas)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.4738	ambiguous
REVEL	0.116	moderately benign-leaning
SaProt	LLR -5.43	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	23.1	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 0.0682% South Asian · 62/90,936 alleles

Filtering AF 0.0545% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0496%

Overall 0.00587% 94/1,600,778 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0682%	1,467
Admixed American	0.047%	2,129
Remaining individualsnot grpmax-eligible	0.00162%	61,652
European (non-Finnish)	0.000256%	391,042

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.Arg772Ser
Coding: c.2314C>A
MANE Select: NM_004062
dbSNP: rs781254169
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.Arg772Cys 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-arg772ser (accessed [today's date]).

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