Is CPS1 p.Asp52Asn (c.154G>A) pathogenic?

CPS1 p.Asp52Asn (c.154G>A) is classified Conflicting classifications of pathogenicity in CPS1 (ClinVar, Conflicting submitters, 4 submitters; last evaluated 2026-01-16). AlphaMissense: likely benign (0.1221); Ultra-rare (popmax 0.0813%, afr); Associated with Inborn genetic diseases.

What condition is associated with CPS1 p.Asp52Asn (c.154G>A)?

CPS1 p.Asp52Asn (c.154G>A) is associated with Inborn genetic diseases, carbamoyl phosphate synthetase I deficiency disease (ClinVar).

How common is CPS1 p.Asp52Asn (c.154G>A) in the general population?

CPS1 p.Asp52Asn (c.154G>A) is ultra-rare (popmax 0.0813%, afr) (gnomAD).

What do computational predictors say about CPS1 p.Asp52Asn (c.154G>A)?

AlphaMissense predicts likely benign (score 0.1221) — an in-silico prediction, not a clinical call.

CPS1 p.Asp52Asn

c.154G>A · rs141481633 · VCV966243

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 4 submitters

AlphaMissense

likely benign

0.1221 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0813%, afr)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1221	likely benign
REVEL	0.7	pathogenic-leaning
SaProt	LLR -8.75	tolerated
⇒ REVEL calls this damaging; AlphaMissense and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2.7, phastCons 1
Regional constraint	o/e 0.93	unconstrained · MANE · 121 kb · p 0.0019 · regional, not allelic
Overall
CADD	28.5	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 0.0813% African / African-American · 61/74,994 alleles

Filtering AF 0.0649% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0591%

Overall 0.00626% 101/1,613,184 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0813%	1,229
Admixed American	0.0434%	2,307
Remaining individualsnot grpmax-eligible	0.0192%	5,205
South Asian	0.0022%	45,536

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.Asp52Asn
Coding: c.154G>A
MANE Select: NM_001875
dbSNP: rs141481633
Type: single nucleotide variant
Location: chr2:210573325 (GRCh38)
Gene constraint: LOEUF 0.764 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 93.80 · 14 PDB
Residue 52: the 'anthranilate phosphoribosyltransferase homolog' region

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.Asp52Gly Uncertain significance ★ ⚠ 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-asp52asn (accessed [today's date]).

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