What condition is associated with CA5A p.Pro151= (c.453C>T)?

CA5A p.Pro151= (c.453C>T) is associated with hyperammonemic encephalopathy due to carbonic anhydrase VA deficiency (ClinVar).

CA5A p.Pro151=

Q: Is CA5A p.Pro151= (c.453C>T) pathogenic?

CA5A p.Pro151= (c.453C>T) is classified Benign in CA5A (ClinVar, Multiple submitters, 5 submitters; last evaluated 2026-02-01). Common (popmax 28.3%, sas) — too common for a highly-penetrant pathogenic allele; Associated with hyperammonemic encephalopathy due to carbonic anhydrase VA deficiency.

Q: How common is CA5A p.Pro151= (c.453C>T) in the general population?

CA5A p.Pro151= (c.453C>T) is common (popmax 28.3%, sas) — too common for a highly-penetrant pathogenic allele (gnomAD).

Q: How is Hyperammonemic encephalopathy due to carbonic anhydrase VA deficiency inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

c.453C>T · rs7186698 · VCV379954

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

gnomAD v4.1

Common

common (popmax 28.3%, sas) — too common for a highly-penetrant pathogenic allele

Conditions

hyperammonemic encephalopathy due to carbonic anhydrase VA deficiency

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -20	GERP -3.9
Overall
CADD	0.22	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 28.3% South Asian · 25,622/90,624 alleles

Filtering AF 28% ClinGen BA1/BS1 input FAF95, joint · FAF99 27.9%

Overall 19.5% 310,532/1,595,794 alleles · common

Ancestry group	Frequency	1 in
South Asiangrpmax	28.3%	4
Amishnot grpmax-eligible	27.5%	4
Ashkenazi Jewishnot grpmax-eligible	23.9%	4
Finnishnot grpmax-eligible	21.1%	5
Middle Eastern	21%	5
Remaining individualsnot grpmax-eligible	19.8%	5
European (non-Finnish)	19.7%	5
East Asian	15.9%	6
Admixed American	12%	8
African / African-American	9.24%	11

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: CA5A
Protein: p.Pro151=
Coding: c.453C>T
MANE Select: NM_001739
dbSNP: rs7186698
Type: single nucleotide variant
Location: chr16:87904792 (GRCh38)
Gene constraint: LOEUF 1.257 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 84.38
Residue 151: the alpha-carbonic anhydrase domain

Full CA5A gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

hyperammonemic encephalopathy due to carbonic anhydrase VA deficiency — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Hyperammonemic encephalopathy due to carbonic anhydrase VA deficiency (Orphanet):

Inheritance: Autosomal recessive
Onset: Childhood, Infancy, Neonatal

Similar variants

CA5A p.Arg32Ter Pathogenic ★★ same condition
CA5A p.Glu241Lys Pathogenic/Likely pathogenic ★★ same condition
CA5A p.Ala149Thr Uncertain significance ★★ ⚠ same condition
CA5A p.Ala208Val Uncertain significance ★★ ⚠ same condition
CA5A p.Ala261Val Uncertain significance ★★ ⚠ same condition
CA5A p.Arg26His Uncertain significance ★★ ⚠ same condition
CA5A p.Asp216Ala Uncertain significance ★★ ⚠ same condition
CA5A p.Gln79Glu Uncertain significance ★★ ⚠ 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/ca5a-p-pro151 (accessed [today's date]).

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