Is VSX2 p.Arg310Pro (c.929G>C) pathogenic?

VSX2 p.Arg310Pro (c.929G>C) is classified Uncertain significance in VSX2 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-08-16). AlphaMissense: likely pathogenic (0.9989); Very rare (popmax 0.00537%, afr); Associated with Inborn genetic diseases.

What condition is associated with VSX2 p.Arg310Pro (c.929G>C)?

VSX2 p.Arg310Pro (c.929G>C) is associated with Inborn genetic diseases (ClinVar).

How common is VSX2 p.Arg310Pro (c.929G>C) in the general population?

VSX2 p.Arg310Pro (c.929G>C) is very rare (popmax 0.00537%, afr) (gnomAD).

What do computational predictors say about VSX2 p.Arg310Pro (c.929G>C)?

AlphaMissense predicts likely pathogenic (score 0.9989) — an in-silico prediction, not a clinical call.

VSX2 p.Arg310Pro

c.929G>C · rs771709336 · VCV2408061

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9989 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00537%, afr)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.9989	likely pathogenic
REVEL	0.887	moderately pathogenic-leaning
SaProt	LLR -18.87	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 12	GERP 2, phastCons 1
Regional constraint	o/e 1.04	unconstrained · MANE · 21 kb · p 0.43 · regional, not allelic
Overall
CADD	34.0	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

Grpmax group 0.00537% African / African-American · 4/74,524 alleles

Filtering AF 0.00175% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00104%

Overall 0.000252% 4/1,587,010 alleles · very rare exomes 3/1,434,812 · genomes 1/152,198 · joint denominator

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.Arg310Pro
Coding: c.929G>C
MANE Select: NM_182894
dbSNP: rs771709336
Type: single nucleotide variant
Location: chr14:74260762 (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

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

VSX2 p.Arg310= Likely benign ★ same residue
VSX2 p.Arg199His Uncertain significance ★★ ⚠ same condition
VSX2 p.Arg206Gln Uncertain significance ★★ ⚠ same condition
VSX2 p.Arg274His Uncertain significance ★★ ⚠ same condition
VSX2 p.Arg288Gln Uncertain significance ★★ ⚠ same condition
VSX2 p.Arg332Trp Uncertain significance ★★ ⚠ same condition
VSX2 p.Pro45Leu Uncertain significance ★★ ⚠ same condition
VSX2 p.Ala294Val 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-arg310pro (accessed [today's date]).

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