Is CDS2 p.Ser440Cys (c.1319C>G) pathogenic?

CDS2 p.Ser440Cys (c.1319C>G) is classified Uncertain significance in CDS2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-04-20). AlphaMissense: likely benign (0.0957); Absent from gnomAD v4.1.

How common is CDS2 p.Ser440Cys (c.1319C>G) in the general population?

CDS2 p.Ser440Cys (c.1319C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CDS2 p.Ser440Cys (c.1319C>G)?

AlphaMissense predicts likely benign (score 0.0957) — an in-silico prediction, not a clinical call.

CDS2 p.Ser440Cys

c.1319C>G · rs2515166908 · VCV2539657

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0957 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0957	likely benign
REVEL	0.052	moderately benign-leaning
SaProt	LLR -10.59	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2	GERP 0.83, phastCons 0.83
Regional constraint	o/e 1.18	unconstrained · MANE · 59 bp · p 0.33 · regional, not allelic
Overall
CADD	17.33	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: CDS2
Protein: p.Ser440Cys
Coding: c.1319C>G
MANE Select: NM_003818
dbSNP: rs2515166908
Type: single nucleotide variant
Location: chr20:5190215 (GRCh38)
Gene constraint: LOEUF 0.944 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.70

Full CDS2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CDS2 p.Ser440Ala Likely benign ★ same residue
CDS2 p.Ala346Ser Uncertain significance ★ ⚠ same type
CDS2 p.Ala398Thr Uncertain significance ★ ⚠ same type
CDS2 p.Arg167Trp Uncertain significance ★ ⚠ same type
CDS2 p.Arg311His Uncertain significance ★ ⚠ same type
CDS2 p.Arg429Gln Uncertain significance ★ ⚠ same type
CDS2 p.Asn426Ser Uncertain significance ★ ⚠ same type
CDS2 p.Asp147Gly Uncertain significance ★ ⚠ 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/cds2-p-ser440cys (accessed [today's date]).

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