Is VSX2 p.Arg200= (c.600A>G) pathogenic?

VSX2 p.Arg200= (c.600A>G) is classified Likely benign in VSX2 (ClinVar, Single submitter, 1 submitter; last evaluated 2020-11-11). Very rare (popmax 0.000593%, nfe); Associated with isolated microphthalmia 2.

What condition is associated with VSX2 p.Arg200= (c.600A>G)?

VSX2 p.Arg200= (c.600A>G) is associated with isolated microphthalmia 2 (ClinVar).

How common is VSX2 p.Arg200= (c.600A>G) in the general population?

VSX2 p.Arg200= (c.600A>G) is very rare (popmax 0.000593%, nfe) (gnomAD).

VSX2 p.Arg200=

c.600A>G · rs536048201 · VCV1589703

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.000593%, nfe)

Conditions

isolated microphthalmia 2

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 1.3	GERP -3, phastCons 1
Overall
CADD	8.82	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000593% European (non-Finnish) · 7/1,180,024 alleles

Filtering AF 0.000247% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000159%

Overall 0.000558% 9/1,614,050 alleles · very rare

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0032%	31,244
European (non-Finnish)grpmax	0.000593%	168,575

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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: VSX2
Protein: p.Arg200=
Coding: c.600A>G
MANE Select: NM_182894
dbSNP: rs536048201
Type: single nucleotide variant
Location: chr14:74259622 (GRCh38)
Gene constraint: LOEUF 1.35 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 61.65
Residue 200: a UniProt-annotated variant site (in mcopcti; loss of dna binding capacity); a UniProt-annotated variant site (in mcopcti; loss of dna binding capacity at consensus sequences; abnormal and prolonged expression of mitf and wls; mislocalization of ctnnb1); a DNA-binding region

Full VSX2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

isolated microphthalmia 2 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

VSX2 p.Arg200Gln Pathogenic ★★ same residue
VSX2 p.Arg200Pro Pathogenic/Likely pathogenic ★★ same residue
VSX2 p.Arg200Ter Pathogenic ★★ same residue
VSX2 c.371-1G>A Pathogenic ★★ same condition
VSX2 p.Arg227Trp Pathogenic/Likely pathogenic ★★ same condition
VSX2 p.Cys29Ter Pathogenic/Likely pathogenic ★★ same condition
VSX2 p.Gln197Ter Pathogenic/Likely pathogenic ★★ same condition
VSX2 p.Trp195Ter Pathogenic/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/vsx2-p-arg200 (accessed [today's date]).

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