Is CDS1 p.Ser424Asn (c.1271G>A) pathogenic?

CDS1 p.Ser424Asn (c.1271G>A) is classified Benign in CDS1 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-10-28). AlphaMissense: likely benign (0.1785); Rare (popmax 0.732%, afr); Associated with CDS1-related disorder.

What condition is associated with CDS1 p.Ser424Asn (c.1271G>A)?

CDS1 p.Ser424Asn (c.1271G>A) is associated with CDS1-related disorder (ClinVar).

How common is CDS1 p.Ser424Asn (c.1271G>A) in the general population?

CDS1 p.Ser424Asn (c.1271G>A) is rare (popmax 0.732%, afr) (gnomAD).

What do computational predictors say about CDS1 p.Ser424Asn (c.1271G>A)?

AlphaMissense predicts likely benign (score 0.1785) — an in-silico prediction, not a clinical call.

CDS1 p.Ser424Asn

c.1271G>A · rs148659910 · VCV3045809

Benign No assertion criteria

Classification

Benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1785 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.732%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

CDS1-related disorder

Computational evidence

Protein change
AlphaMissense	0.1785	likely benign
REVEL	0.115	moderately benign-leaning
SaProt	LLR -6.81	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 12	GERP 2.5, phastCons 1
Overall
CADD	24.1	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 0.732% African / African-American · 549/74,994 alleles

Filtering AF 0.681% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.661%

Overall 0.0403% 650/1,613,244 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.732%	137
Middle Eastern	0.132%	757
Remaining individualsnot grpmax-eligible	0.0704%	1,420
Admixed American	0.0617%	1,620
South Asian	0.0022%	45,416
European (non-Finnish)	0.000848%	117,963

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: CDS1
Protein: p.Ser424Asn
Coding: c.1271G>A
MANE Select: NM_007194 · reported on NM_001263
dbSNP: rs148659910
Type: single nucleotide variant
Location: chr4:84648571 (GRCh38)
Structure: AlphaFold pLDDT 77.64 · 38 PDB
Residue 424: the protein kinase domain

Full CDS1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

CDS1-related disorder

Similar variants

CHEK2 p.Tyr424Ter Pathogenic ★★ same residue
CHEK2 p.Tyr424= Benign/Likely benign ★★ same residue
CHEK2 p.Tyr424Cys Uncertain significance ★ ⚠ same residue
CHEK2 p.Tyr424His Conflicting classifications of pathogenicity ★ ⚠ same residue
CHEK2 c.319+2T>A Pathogenic/Likely pathogenic ★★ same condition
CHEK2 c.444+1G>A Pathogenic/Likely pathogenic ★★ same condition
CHEK2 c.592+3A>T Pathogenic/Likely pathogenic ★★ same condition
CHEK2 c.593-1G>T Pathogenic/Likely pathogenic ★★ 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/cds1-p-ser424asn (accessed [today's date]).

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