Is CA4 p.Lys267Arg (c.800A>G) pathogenic?

CA4 p.Lys267Arg (c.800A>G) is classified Conflicting classifications of pathogenicity in CA4 (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2024-02-20). AlphaMissense: likely benign (0.0962); Rare (popmax 0.114%, eas); Associated with inherited retinal dystrophy.

What condition is associated with CA4 p.Lys267Arg (c.800A>G)?

CA4 p.Lys267Arg (c.800A>G) is associated with inherited retinal dystrophy (ClinVar).

How common is CA4 p.Lys267Arg (c.800A>G) in the general population?

CA4 p.Lys267Arg (c.800A>G) is rare (popmax 0.114%, eas) (gnomAD).

What do computational predictors say about CA4 p.Lys267Arg (c.800A>G)?

AlphaMissense predicts likely benign (score 0.0962) — an in-silico prediction, not a clinical call.

CA4 p.Lys267Arg

c.800A>G · rs187221698 · VCV1385601

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.0962 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.114%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

inherited retinal dystrophy

Computational evidence

Protein change
AlphaMissense	0.0962	likely benign
REVEL	0.175	moderately benign-leaning
SaProt	LLR -7.04	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	GERP -2.3
Regional constraint	o/e 0.99	unconstrained · MANE · 9,386 bp · p 0.89 · regional, not allelic
Overall
CADD	9.223	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

Grpmax group 0.114% East Asian · 51/44,714 alleles

Filtering AF 0.0891% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0802%

Overall 0.00335% 54/1,610,380 alleles · rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.114%	877
Remaining individualsnot grpmax-eligible	0.00481%	20,777

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: CA4
Protein: p.Lys267Arg
Coding: c.800A>G
MANE Select: NM_000717
dbSNP: rs187221698
Type: single nucleotide variant
Location: chr17:60159285 (GRCh38)
Gene constraint: LOEUF 0.975 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 89.86 · 10 PDB
Residue 267: 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.Lys267Asn Uncertain significance ★ ⚠ 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-lys267arg (accessed [today's date]).

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