Is CDAN1 p.Pro268Ser (c.802C>T) pathogenic?

CDAN1 p.Pro268Ser (c.802C>T) is classified Uncertain significance in CDAN1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-08-07). AlphaMissense: likely benign (0.0684); Very rare (popmax 0.000169%, nfe).

How common is CDAN1 p.Pro268Ser (c.802C>T) in the general population?

CDAN1 p.Pro268Ser (c.802C>T) is very rare (popmax 0.000169%, nfe) (gnomAD).

What do computational predictors say about CDAN1 p.Pro268Ser (c.802C>T)?

AlphaMissense predicts likely benign (score 0.0684) — an in-silico prediction, not a clinical call.

CDAN1 p.Pro268Ser

c.802C>T · rs759337775 · VCV3002320

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0684 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000169%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0684	likely benign
REVEL	0.271	benign-leaning
SaProt	LLR -6.86	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 5.1	GERP 2.3, phastCons 1
Regional constraint	o/e 1.15	unconstrained · MANE · 1,562 bp · p 0.0016 · regional, not allelic
Overall
CADD	18.16	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000169% European (non-Finnish) · 2/1,180,022 alleles

Filtering AF 2.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000137% 2/1,461,826 alleles · very rare

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.Pro268Ser
Coding: c.802C>T
MANE Select: NM_138477
dbSNP: rs759337775
Type: single nucleotide variant
Location: chr15:42735651 (GRCh38)
Gene constraint: LOEUF 0.908 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 72.58 · 2 PDB
Residue 268: the 'disordered' region

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

Similar variants

CDAN1 p.Pro268Arg Uncertain significance ★★ ⚠ same residue
CDAN1 p.Pro268= Benign/Likely benign ★★ 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
CDAN1 p.Pro1130Leu 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-pro268ser (accessed [today's date]).

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