Is CDAN1 p.Ser701Pro (c.2101T>C) pathogenic?

CDAN1 p.Ser701Pro (c.2101T>C) is classified Uncertain significance in CDAN1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-22). AlphaMissense: likely pathogenic (0.9488); Very rare (popmax 0.000508%, nfe); Associated with Inborn genetic diseases.

What condition is associated with CDAN1 p.Ser701Pro (c.2101T>C)?

CDAN1 p.Ser701Pro (c.2101T>C) is associated with Inborn genetic diseases (ClinVar).

How common is CDAN1 p.Ser701Pro (c.2101T>C) in the general population?

CDAN1 p.Ser701Pro (c.2101T>C) is very rare (popmax 0.000508%, nfe) (gnomAD).

What do computational predictors say about CDAN1 p.Ser701Pro (c.2101T>C)?

AlphaMissense predicts likely pathogenic (score 0.9488) — an in-silico prediction, not a clinical call.

CDAN1 p.Ser701Pro

c.2101T>C · rs144339527 · VCV2397691

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9488 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000508%, nfe)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.9488	likely pathogenic · top 6% in CDAN1
REVEL	0.895	moderately pathogenic-leaning
SaProt	LLR -16.52	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 8	GERP 2, phastCons 1
Regional constraint	o/e 1.11	unconstrained · MANE · 7,202 bp · p 0.0016 · regional, not allelic
Overall
CADD	26.1	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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 0.000508% European (non-Finnish) · 6/1,180,036 alleles

Filtering AF 0.000183% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00012%

Overall 0.000372% 6/1,614,020 alleles · very rare exomes 5/1,461,784 · genomes 1/152,236 · joint denominator

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.Ser701Pro
Coding: c.2101T>C
MANE Select: NM_138477
dbSNP: rs144339527
Type: single nucleotide variant
Location: chr15:42730671 (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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CDAN1 p.Ser701Cys Uncertain significance ★ ⚠ same residue
CDAN1 p.Ser701= Likely benign ★ same residue
CDAN1 p.Ala1110Gly Uncertain significance ★★ ⚠ same condition
CDAN1 p.Ala887Glu Uncertain significance ★★ ⚠ same condition
CDAN1 p.Ala973Ser Uncertain significance ★★ ⚠ same condition
CDAN1 p.Arg1010Gln Uncertain significance ★★ ⚠ same condition
CDAN1 p.Arg282Gln Uncertain significance ★★ ⚠ same condition
CDAN1 p.Arg688Gln Uncertain significance ★★ ⚠ same condition

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-ser701pro (accessed [today's date]).

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