Is VSX2 p.Ter362= (c.1086G>A) pathogenic?

VSX2 p.Ter362= (c.1086G>A) is classified Likely benign in VSX2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-29). Very rare (popmax 0.00387%, amr); Associated with isolated microphthalmia 2.

What condition is associated with VSX2 p.Ter362= (c.1086G>A)?

VSX2 p.Ter362= (c.1086G>A) is associated with isolated microphthalmia 2 (ClinVar).

How common is VSX2 p.Ter362= (c.1086G>A) in the general population?

VSX2 p.Ter362= (c.1086G>A) is very rare (popmax 0.00387%, amr) (gnomAD).

VSX2 p.Ter362=

c.1086G>A · rs1193237728 · VCV1091066

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

stop-loss

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00387%, amr)

Conditions

isolated microphthalmia 2

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	stop-loss	predicted loss-of-function
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5	GERP -2.2, phastCons 1
Overall
CADD	10.53	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00387% Admixed American · 2/51,734 alleles

Filtering AF 0.00125% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00107%

Overall 0.00154% 24/1,555,724 alleles · very rare exomes 24/1,403,410 · genomes 0/152,314 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00387%	25,867
European (non-Finnish)	0.00191%	52,297

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.Ter362=
Coding: c.1086G>A
MANE Select: NM_182894
dbSNP: rs1193237728
Type: single nucleotide variant
Location: chr14:74260919 (GRCh38)
Gene constraint: LOEUF 1.35 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 61.65

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.Ter362Tyr Likely pathogenic ★ same residue
VSX2 c.371-1G>A Pathogenic ★★ same condition
VSX2 p.Arg200Gln Pathogenic ★★ same condition
VSX2 p.Arg200Pro Pathogenic/Likely pathogenic ★★ same condition
VSX2 p.Arg200Ter 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

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-ter362 (accessed [today's date]).

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