Is CA4 p.Thr263Arg (c.788C>G) pathogenic?

CA4 p.Thr263Arg (c.788C>G) is classified Likely benign in CA4 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-10-01). AlphaMissense: likely benign (0.0899); Absent from gnomAD v4.1; Associated with inherited retinal dystrophy.

What condition is associated with CA4 p.Thr263Arg (c.788C>G)?

CA4 p.Thr263Arg (c.788C>G) is associated with inherited retinal dystrophy (ClinVar).

How common is CA4 p.Thr263Arg (c.788C>G) in the general population?

CA4 p.Thr263Arg (c.788C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CA4 p.Thr263Arg (c.788C>G)?

AlphaMissense predicts likely benign (score 0.0899) — an in-silico prediction, not a clinical call.

CA4 p.Thr263Arg

c.788C>G · rs777166953 · VCV3028477

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0899 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

inherited retinal dystrophy

Computational evidence

Protein change
AlphaMissense	0.0899	likely benign
REVEL	0.024	moderately benign-leaning
SaProt	LLR -5.62	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 -2.1	GERP -2.3
Regional constraint	o/e 0.99	unconstrained · MANE · 9,386 bp · p 0.89 · regional, not allelic
Overall
CADD	0.005	PHRED · no single calibrated threshold — expert panels disagree

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: CA4
Protein: p.Thr263Arg
Coding: c.788C>G
MANE Select: NM_000717
dbSNP: rs777166953
Type: single nucleotide variant
Location: chr17:60159273 (GRCh38)
Gene constraint: LOEUF 0.975 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 89.86 · 10 PDB
Residue 263: the alpha-carbonic anhydrase domain

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.Thr263Ala Conflicting classifications of pathogenicity ★ ⚠ same residue
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

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-thr263arg (accessed [today's date]).

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