Is CA4 p.Ala167= (c.501C>G) pathogenic?

CA4 p.Ala167= (c.501C>G) is classified Uncertain significance in CA4 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-10-01). Absent from gnomAD v4.1; Associated with inherited retinal dystrophy.

What condition is associated with CA4 p.Ala167= (c.501C>G)?

CA4 p.Ala167= (c.501C>G) is associated with inherited retinal dystrophy (ClinVar).

How common is CA4 p.Ala167= (c.501C>G) in the general population?

CA4 p.Ala167= (c.501C>G) is absent from gnomAD v4.1 (gnomAD).

CA4 p.Ala167=

c.501C>G · rs2544521475 · VCV3028473

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

inherited retinal dystrophy

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 0.083	GERP 0.57, phastCons 0.89
Overall
CADD	7.751	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: CA4
Protein: p.Ala167=
Coding: c.501C>G
MANE Select: NM_000717
dbSNP: rs2544521475
Type: single nucleotide variant
Location: chr17:60157776 (GRCh38)
Gene constraint: LOEUF 0.975 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 89.86 · 10 PDB
Residue 167: a disulfide bond; the alpha-carbonic anhydrase domain; a β-strand

Full CA4 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

inherited retinal dystrophy — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CA4 p.Asp268Asn Uncertain significance ★★ ⚠ same condition
CA4 p.Ala164= Benign/Likely benign ★★ same condition
CA4 p.Asn177Lys Benign/Likely benign ★★ same condition
CA4 p.Asp161= Likely benign ★★ same condition
CA4 p.Lys145= Benign/Likely benign ★★ same condition
CA4 p.Pro287= Benign/Likely benign ★★ same condition
CA4 p.Ser119= Benign/Likely benign ★★ same condition
CA4 p.Cys229Ter 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/ca4-p-ala167 (accessed [today's date]).

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