What condition is associated with CA5A p.Ala269= (c.807A>T)?

CA5A p.Ala269= (c.807A>T) is associated with hyperammonemic encephalopathy due to carbonic anhydrase VA deficiency (ClinVar).

CA5A p.Ala269=

Q: Is CA5A p.Ala269= (c.807A>T) pathogenic?

CA5A p.Ala269= (c.807A>T) is classified Benign in CA5A (ClinVar, Multiple submitters, 6 submitters; last evaluated 2026-02-03). Common (popmax 26.3%, 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.Ala269= (c.807A>T) in the general population?

CA5A p.Ala269= (c.807A>T) is common (popmax 26.3%, 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.807A>T · rs72816311 · VCV379955

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

gnomAD v4.1

Common

common (popmax 26.3%, 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 -15	GERP -3.7
Overall
CADD	0.016	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 26.3% South Asian · 23,953/91,040 alleles

Filtering AF 26% ClinGen BA1/BS1 input FAF95, joint · FAF99 25.9%

Overall 19.5% 315,225/1,613,382 alleles · common

Ancestry group	Frequency	1 in
South Asiangrpmax	26.3%	4
Ashkenazi Jewishnot grpmax-eligible	26.2%	4
Middle Eastern	20.7%	5
Remaining individualsnot grpmax-eligible	20.1%	5
European (non-Finnish)	20%	5
Amishnot grpmax-eligible	15.8%	6
Finnishnot grpmax-eligible	14.9%	7
African / African-American	13.7%	7
East Asian	13.6%	7
Admixed American	12.4%	8

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.Ala269=
Coding: c.807A>T
MANE Select: NM_001739
dbSNP: rs72816311
Type: single nucleotide variant
Location: chr16:87888240 (GRCh38)
Gene constraint: LOEUF 1.257 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 84.38
Residue 269: 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-ala269 (accessed [today's date]).

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