Is CDS1 p.Phe337Ser (c.1010T>C) pathogenic?

CDS1 p.Phe337Ser (c.1010T>C) is classified Uncertain significance in CDS1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-31). AlphaMissense: likely benign (0.1475); Absent from gnomAD v4.1.

How common is CDS1 p.Phe337Ser (c.1010T>C) in the general population?

CDS1 p.Phe337Ser (c.1010T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CDS1 p.Phe337Ser (c.1010T>C)?

AlphaMissense predicts likely benign (score 0.1475) — an in-silico prediction, not a clinical call.

CDS1 p.Phe337Ser

c.1010T>C · VCV4224870

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1475 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,597,262)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1475	likely benign
REVEL	0.103	moderately benign-leaning
SaProt	LLR -8.39	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 6.1	GERP 1.4, phastCons 1
Overall
CADD	20.6	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — 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

No allele count reported in gnomAD v4.1 (AN 1,597,262). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: CDS1
Protein: p.Phe337Ser
Coding: c.1010T>C
MANE Select: NM_007194 · reported on NM_001263
Type: single nucleotide variant
Location: chr4:84640968 (GRCh38)
Structure: AlphaFold pLDDT 77.64 · 38 PDB
Residue 337: an α-helix; the protein kinase domain

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

Similar variants

CHEK2 p.Tyr337Ter Pathogenic/Likely pathogenic ★★ same residue
CHEK2 p.Tyr337Asp Uncertain significance ★ ⚠ same residue
CHEK2 p.Tyr337Cys Uncertain significance ★ ⚠ same residue
CHEK2 p.Tyr337His Uncertain significance ★ ⚠ same residue
CHEK2 p.Tyr337Phe Uncertain significance ★ ⚠ same residue
CHEK2 c.1008+1G>A Likely pathogenic ★★ same type
CHEK2 c.1008+1G>T Likely pathogenic ★★ same type
CHEK2 c.1008+2T>A Likely pathogenic ★★ 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/cds1-p-phe337ser (accessed [today's date]).

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