Is CA5A p.Glu138= (c.414G>A) pathogenic?

CA5A p.Glu138= (c.414G>A) is classified Likely benign in CA5A (ClinVar, Single submitter, 1 submitter; last evaluated 2024-06-12). Absent from gnomAD v4.1; Associated with hyperammonemic encephalopathy due to carbonic anhydrase VA deficiency.

What condition is associated with CA5A p.Glu138= (c.414G>A)?

CA5A p.Glu138= (c.414G>A) is associated with hyperammonemic encephalopathy due to carbonic anhydrase VA deficiency (ClinVar).

How common is CA5A p.Glu138= (c.414G>A) in the general population?

CA5A p.Glu138= (c.414G>A) is absent from gnomAD v4.1 (gnomAD).

CA5A p.Glu138=

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.414G>A · VCV3611932

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

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	<0.2	all four deltas below 0.2 · C>G here scores Δ0.20 · evaluated, not missing
Constraint at this position
Conservation	phyloP -0.62	GERP -3.9
Overall
CADD	2.259	PHRED · no single calibrated threshold — expert panels disagree

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: CA5A
Protein: p.Glu138=
Coding: c.414G>A
MANE Select: NM_001739
Type: single nucleotide variant
Location: chr16:87904831 (GRCh38)
Gene constraint: LOEUF 1.257 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 84.38
Residue 138: 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.Glu138Lys Uncertain significance ★ ⚠ same residue
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

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-glu138 (accessed [today's date]).

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