MYOC p.Arg320=
c.960G>A · rs2527839502 · VCV1810369
ClinGen expert panel — Glaucoma VCEP
Uncertain Significance for open-angle glaucoma. Applied ACMG criteria (verbatim):
PM2_Supporting BP7 BP4
Curation rationale (ClinGen, verbatim)
The c.960G>A variant in MYOC is a synonymous variant (p.Arg320=). This variant was not found in any genetic ancestry group of gnomAD (v4.1.0), meeting the ≤ 0.0001 threshold set for PM2_Supporting in a genetic ancestry group of at least 10,000 alleles. The SpliceAI score = 0, which met the ≤ 0.1 threshold for BP4, suggesting that the variant does not impact MYOC function. This synonymous variant meets BP4, so BP7 is met. There was no functional evidence predicting a damaging or benign impact of this variant on MYOC function. Only 1 proband with primary open angle glaucoma had been reported (ANZRAG [E Souzeau pers. comm.]), not meeting the ≥ 2 probands threshold required to meet PS4_Supporting. In summary, this variant met the criteria to receive a score of -1 and to be classified as a variant of uncertain significance (uncertain significance classification range -1 to 5, adapted from PMID: 32720330) for primary open angle glaucoma based on the ACMG/AMP criteria met, as specified by the ClinGen Glaucoma VCEP (v2.0.0, 5 Dec 2024): PM2_Supporting, BP4, BP7
ClinGen Evidence Repository → · reported verbatim, not re-tallied by Sugi Variant.
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 0.57 | phastCons 0.002 |
| Overall | ||
| CADD | 4.769 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
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
- MYOC
- Protein
- p.Arg320=
- Coding
- c.960G>A
- MANE Select
- NM_000261
- dbSNP
- rs2527839502
- Type
- single nucleotide variant
- Location
- chr1:171636480 (GRCh38)
- Gene constraint
- LOEUF 1.343 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 79.40 · 24 PDB
- Residue 320
- the olfactomedin-like domain
Similar variants
- MYOC p.Ala363Thr Likely pathogenic ★★★ same condition
- MYOC p.Arg272Gly Likely pathogenic ★★★ same condition
- MYOC p.Asn450Tyr Likely pathogenic ★★★ same condition
- MYOC p.Asn480Lys Pathogenic ★★★ same condition
- MYOC p.Asp380Ala Pathogenic ★★★ same condition
- MYOC p.Asp380Gly Likely pathogenic ★★★ same condition
- MYOC p.Asp380His Likely pathogenic ★★★ same condition
- MYOC p.Asp380Tyr 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/myoc-p-arg320 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown