Is CA5A p.Ile203Val (c.607A>G) pathogenic?

CA5A p.Ile203Val (c.607A>G) is classified Uncertain significance in CA5A (ClinVar, Single submitter, 1 submitter; last evaluated 2024-06-22). AlphaMissense: likely benign (0.1273); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with CA5A p.Ile203Val (c.607A>G)?

CA5A p.Ile203Val (c.607A>G) is associated with Inborn genetic diseases (ClinVar).

How common is CA5A p.Ile203Val (c.607A>G) in the general population?

CA5A p.Ile203Val (c.607A>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CA5A p.Ile203Val (c.607A>G)?

AlphaMissense predicts likely benign (score 0.1273) — an in-silico prediction, not a clinical call.

CA5A p.Ile203Val

c.607A>G · VCV3262588

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1273 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1273	likely benign
REVEL	0.179	moderately benign-leaning
SaProt	LLR -7.90	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.4	GERP 1.8, phastCons 0.94
Regional constraint	o/e 1.11	unconstrained · MANE · 48 kb · p 0.027 · regional, not allelic
Overall
CADD	5.889	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

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.Ile203Val
Coding: c.607A>G
MANE Select: NM_001739
Type: single nucleotide variant
Location: chr16:87901923 (GRCh38)
Gene constraint: LOEUF 1.257 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 84.38
Residue 203: the alpha-carbonic anhydrase domain

Full CA5A 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

Similar variants

CA5A p.Ala149Thr Uncertain significance ★★ ⚠ same condition
CA5A p.His143Asp Uncertain significance ★★ ⚠ same condition
CA5A p.Leu259Val Uncertain significance ★★ ⚠ same condition
CA5A p.Phe215Ile Uncertain significance ★★ same condition
CA5A p.Pro222Ser Uncertain significance ★★ ⚠ same condition
CA5A p.Pro30Arg Uncertain significance ★★ ⚠ same condition
CA5A p.Thr192Met Uncertain significance ★★ ⚠ same condition
CA5A p.Thr223Asn 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-ile203val (accessed [today's date]).

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