Is CDAN1 p.Arg1111Pro (c.3332G>C) pathogenic?

CDAN1 p.Arg1111Pro (c.3332G>C) is classified Uncertain significance in CDAN1 (ClinVar, Single submitter, 1 submitter; last evaluated 2016-08-10). AlphaMissense: likely benign (0.3275); Very rare (popmax 0.0022%, sas).

How common is CDAN1 p.Arg1111Pro (c.3332G>C) in the general population?

CDAN1 p.Arg1111Pro (c.3332G>C) is very rare (popmax 0.0022%, sas) (gnomAD).

What do computational predictors say about CDAN1 p.Arg1111Pro (c.3332G>C)?

AlphaMissense predicts likely benign (score 0.3275) — an in-silico prediction, not a clinical call.

CDAN1 p.Arg1111Pro

c.3332G>C · rs746582832 · VCV421887

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.3275 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0022%, sas)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.3275	likely benign
REVEL	0.435	indeterminate
SaProt	LLR -12.57	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.7	GERP 1.1, phastCons 0.99
Regional constraint	o/e 1.11	unconstrained · MANE · 7,202 bp · p 0.0016 · regional, not allelic
Overall
CADD	22.8	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 0.0022% South Asian · 2/91,082 alleles

Filtering AF 0.000365% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000137%

Overall 0.00041% 6/1,461,882 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0022%	45,541
European (non-Finnish)	0.000339%	295,006

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: CDAN1
Protein: p.Arg1111Pro
Coding: c.3332G>C
MANE Select: NM_138477
dbSNP: rs746582832
Type: single nucleotide variant
Location: chr15:42725607 (GRCh38)
Gene constraint: LOEUF 0.908 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 72.58 · 2 PDB

Full CDAN1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CDAN1 p.Arg1111Gln Uncertain significance ★ ⚠ same residue
CDAN1 p.Arg1111Gly Uncertain significance ★ ⚠ same residue
CDAN1 p.Arg1111fs Pathogenic ★ same residue
CDAN1 p.Arg1042Trp Pathogenic/Likely pathogenic ★★ ⚠ same type
CDAN1 p.Arg682Ter Pathogenic ★★ same type
CDAN1 p.Arg714Trp Pathogenic/Likely pathogenic ★★ ⚠ same type
CDAN1 p.Asn599Ser Likely pathogenic ★★ ⚠ same type
CDAN1 p.Phe52Leu Pathogenic/Likely 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/cdan1-p-arg1111pro (accessed [today's date]).

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