Is CPS1 p.Pro1105Arg (c.3314C>G) pathogenic?

CPS1 p.Pro1105Arg (c.3314C>G) is classified Uncertain significance in CPS1 (ClinVar, Single submitter, 1 submitter; last evaluated 2020-07-03). AlphaMissense: likely benign (0.1949); Absent from gnomAD v4.1.

How common is CPS1 p.Pro1105Arg (c.3314C>G) in the general population?

CPS1 p.Pro1105Arg (c.3314C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CPS1 p.Pro1105Arg (c.3314C>G)?

AlphaMissense predicts likely benign (score 0.1949) — an in-silico prediction, not a clinical call.

CPS1 p.Pro1105Arg

c.3314C>G · VCV4959652

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1949 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.1949	likely benign
REVEL	0.539	indeterminate
SaProt	LLR -11.29	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 1.8, phastCons 1
Regional constraint	o/e 0.93	unconstrained · MANE · 121 kb · p 0.0019 · regional, not allelic
Overall
CADD	22.6	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: CPS1
Protein: p.Pro1105Arg
Coding: c.3314C>G
MANE Select: NM_001875
Type: single nucleotide variant
Location: chr2:210648035 (GRCh38)
Gene constraint: LOEUF 0.764 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 93.80 · 14 PDB
Residue 1105: the atp-grasp 2 domain

Full CPS1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CPS1 p.Pro1105Leu Uncertain significance ★ ⚠ same residue
CPS1 p.Pro1105Ser Conflicting classifications of pathogenicity ★ ⚠ same residue
CPS1 p.Pro1105_Trp1106insTer Likely pathogenic ★ same residue
CPS1 c.1086+1G>A Likely pathogenic ★★ same type
CPS1 c.1087-1G>T Pathogenic/Likely pathogenic ★★ same type
CPS1 c.1165-2A>G Likely pathogenic ★★ same type
CPS1 c.1263+5G>C Pathogenic/Likely pathogenic ★★ same type
CPS1 c.1549+1G>A Pathogenic/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/cps1-p-pro1105arg (accessed [today's date]).

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