Is CDSN p.Ser440Gly (c.1318A>G) pathogenic?

CDSN p.Ser440Gly (c.1318A>G) is classified Likely benign in CDSN (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-19). Very rare (popmax 0.00833%, amr); Associated with Inborn genetic diseases.

What condition is associated with CDSN p.Ser440Gly (c.1318A>G)?

CDSN p.Ser440Gly (c.1318A>G) is associated with Inborn genetic diseases (ClinVar).

How common is CDSN p.Ser440Gly (c.1318A>G) in the general population?

CDSN p.Ser440Gly (c.1318A>G) is very rare (popmax 0.00833%, amr) (gnomAD).

CDSN p.Ser440Gly

c.1318A>G · VCV4610518

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00833%, amr)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.007	strongly benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -1.9
Overall
CADD	0.074	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00833% Admixed American · 5/59,990 alleles

Filtering AF 0.00323% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00207%

Overall 0.000496% 8/1,613,890 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00833%	11,998
Remaining individualsnot grpmax-eligible	0.0032%	31,240
African / African-American	0.00134%	74,870

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.Ser440Gly
Coding: c.1318A>G
MANE Select: NM_001264
Type: single nucleotide variant
Location: chr6:31116297 (GRCh38)
Gene constraint: LOEUF 0.77 · pLI 0.08 (gnomAD)
Structure: AlphaFold pLDDT 38.13
Residue 440: 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.Ser440Arg 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-ser440gly (accessed [today's date]).

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