Is CDSN p.Ala481Thr (c.1441G>A) pathogenic?

CDSN p.Ala481Thr (c.1441G>A) is classified Uncertain significance in CDSN (ClinVar, Single submitter, 2 submitters; last evaluated 2025-01-22). Ultra-rare (popmax 0.0561%, afr); Associated with Inborn genetic diseases.

What condition is associated with CDSN p.Ala481Thr (c.1441G>A)?

CDSN p.Ala481Thr (c.1441G>A) is associated with Inborn genetic diseases (ClinVar).

How common is CDSN p.Ala481Thr (c.1441G>A) in the general population?

CDSN p.Ala481Thr (c.1441G>A) is ultra-rare (popmax 0.0561%, afr) (gnomAD).

CDSN p.Ala481Thr

c.1441G>A · rs138093208 · VCV2392544

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0561%, afr)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.035	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.2	phastCons 0.97
Overall
CADD	18.45	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0561% African / African-American · 42/74,924 alleles

Filtering AF 0.0425% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0379%

Overall 0.0062% 100/1,612,184 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0561%	1,784
Ashkenazi Jewishnot grpmax-eligible	0.0542%	1,845
East Asian	0.00669%	14,949
Admixed American	0.00333%	29,990
Remaining individualsnot grpmax-eligible	0.0032%	31,233
European (non-Finnish)	0.00297%	33,682

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: CDSN
Protein: p.Ala481Thr
Coding: c.1441G>A
MANE Select: NM_001264
dbSNP: rs138093208
Type: single nucleotide variant
Location: chr6:31116174 (GRCh38)
Gene constraint: LOEUF 0.77 · pLI 0.08 (gnomAD)
Structure: AlphaFold pLDDT 38.13
Residue 481: the 'disordered' region

Full CDSN 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

CDSN p.Ala481Ser Uncertain significance ★ same residue
CDSN p.Cys423Ser Uncertain significance ★★ same condition
CDSN p.Gly335Ala Uncertain significance ★★ same condition
CDSN p.Pro226Ser Uncertain significance ★★ same condition
CDSN p.Pro471Leu Uncertain significance ★★ same condition
CDSN p.Ser159Gly Uncertain significance ★★ same condition
CDSN p.Ser274Asn Uncertain significance ★★ same condition
CDSN p.Val506Met 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/cdsn-p-ala481thr (accessed [today's date]).

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