Is VSX2 p.Ala201Asp (c.602C>A) pathogenic?

VSX2 p.Ala201Asp (c.602C>A) is classified Uncertain significance in VSX2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-05-20). AlphaMissense: likely pathogenic (1); Absent from gnomAD v4.1; Associated with microphthalmia, isolated, with coloboma 3.

What condition is associated with VSX2 p.Ala201Asp (c.602C>A)?

VSX2 p.Ala201Asp (c.602C>A) is associated with microphthalmia, isolated, with coloboma 3 (ClinVar).

How common is VSX2 p.Ala201Asp (c.602C>A) in the general population?

VSX2 p.Ala201Asp (c.602C>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about VSX2 p.Ala201Asp (c.602C>A)?

AlphaMissense predicts likely pathogenic (score 1) — an in-silico prediction, not a clinical call.

VSX2 p.Ala201Asp

c.602C>A · VCV3341298

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

1 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

microphthalmia, isolated, with coloboma 3

Computational evidence

Protein change
AlphaMissense	1	likely pathogenic · top 8% in VSX2
REVEL	0.926	moderately pathogenic-leaning
SaProt	LLR -14.55	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 2.2, phastCons 1
Regional constraint	o/e 1.04	unconstrained · MANE · 21 kb · p 0.43 · regional, not allelic
Overall
CADD	32.0	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

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: VSX2
Protein: p.Ala201Asp
Coding: c.602C>A
MANE Select: NM_182894
Type: single nucleotide variant
Location: chr14:74259624 (GRCh38)
Gene constraint: LOEUF 1.35 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 61.65
Residue 201: a DNA-binding region

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

Disease context

microphthalmia, isolated, with coloboma 3 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

VSX2 p.Ala201= Likely benign ★ same residue
VSX2 c.371-1G>A Pathogenic ★★ same condition
VSX2 p.Arg200Pro Pathogenic/Likely pathogenic ★★ same condition
VSX2 p.Arg227Trp Pathogenic/Likely pathogenic ★★ same condition
VSX2 p.Cys29Ter Pathogenic/Likely pathogenic ★★ same condition
VSX2 c.*250C>T Uncertain significance ★★ same condition
VSX2 c.*962G>T Uncertain significance ★★ same condition
VSX2 p.Arg178Gln Uncertain significance ★★ ⚠ 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-ala201asp (accessed [today's date]).

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