Is CPS1 p.Arg238Gln (c.713G>A) pathogenic?

CPS1 p.Arg238Gln (c.713G>A) is classified Uncertain significance in CPS1 (ClinVar, Multiple submitters, 5 submitters; last evaluated 2026-01-14). AlphaMissense: likely benign (0.1386); Ultra-rare (popmax 0.0852%, nfe); Associated with Inborn genetic diseases.

What condition is associated with CPS1 p.Arg238Gln (c.713G>A)?

CPS1 p.Arg238Gln (c.713G>A) is associated with Inborn genetic diseases, carbamoyl phosphate synthetase I deficiency disease (ClinVar).

How common is CPS1 p.Arg238Gln (c.713G>A) in the general population?

CPS1 p.Arg238Gln (c.713G>A) is ultra-rare (popmax 0.0852%, nfe) (gnomAD).

What do computational predictors say about CPS1 p.Arg238Gln (c.713G>A)?

AlphaMissense predicts likely benign (score 0.1386) — an in-silico prediction, not a clinical call.

CPS1 p.Arg238Gln

c.713G>A · rs147294932 · VCV583220

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

AlphaMissense

likely benign

0.1386 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0852%, nfe)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1386	likely benign
REVEL	0.592	indeterminate
SaProt	LLR -11.08	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL makes no call.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>T here scores Δ0.35 · evaluated, not missing
Constraint at this position
Conservation	phyloP 10	GERP 2.9, phastCons 1
Regional constraint	o/e 0.93	unconstrained · MANE · 121 kb · p 0.0019 · regional, not allelic
Overall
CADD	32.0	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 0.0852% European (non-Finnish) · 1,004/1,178,992 alleles

Filtering AF 0.0808% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.079%

Overall 0.0655% 1,057/1,612,580 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0852%	1,174
Remaining individualsnot grpmax-eligible	0.0272%	3,671
Finnishnot grpmax-eligible	0.025%	4,001
African / African-American	0.0227%	4,404
Middle Eastern	0.0165%	6,052
Admixed American	0.00167%	59,920
South Asian	0.0011%	91,052

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: CPS1
Protein: p.Arg238Gln
Coding: c.713G>A
MANE Select: NM_001875
dbSNP: rs147294932
Type: single nucleotide variant
Location: chr2:210590107 (GRCh38)
Gene constraint: LOEUF 0.764 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 93.80 · 14 PDB
Residue 238: the glutamine amidotransferase type-1 domain

Full CPS1 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

Also linked: carbamoyl phosphate synthetase I deficiency disease

Similar variants

CPS1 p.Arg238Ter Pathogenic/Likely pathogenic ★★ same residue
CPS1 c.1086+1G>A Likely pathogenic ★★ same condition
CPS1 c.1087-1G>T Pathogenic/Likely pathogenic ★★ same condition
CPS1 c.1165-2A>G Likely pathogenic ★★ same condition
CPS1 c.1263+5G>C Pathogenic/Likely pathogenic ★★ same condition
CPS1 c.1549+1G>A Pathogenic/Likely pathogenic ★★ same condition
CPS1 c.1549+1G>T Pathogenic/Likely pathogenic ★★ same condition
CPS1 c.1837-8A>G 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/cps1-p-arg238gln (accessed [today's date]).

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