Is MYOC p.Ser313Phe (c.938C>T) pathogenic?

MYOC p.Ser313Phe (c.938C>T) is classified Uncertain significance in MYOC (ClinVar, Expert panel, 1 submitter; last evaluated 2026-01-20). AlphaMissense: likely benign (0.2544); Ultra-rare (popmax 0.029%, eas); Associated with open-angle glaucoma.

What condition is associated with MYOC p.Ser313Phe (c.938C>T)?

MYOC p.Ser313Phe (c.938C>T) is associated with open-angle glaucoma (ClinVar).

How common is MYOC p.Ser313Phe (c.938C>T) in the general population?

MYOC p.Ser313Phe (c.938C>T) is ultra-rare (popmax 0.029%, eas) (gnomAD).

What do computational predictors say about MYOC p.Ser313Phe (c.938C>T)?

AlphaMissense predicts likely benign (score 0.2544) — an in-silico prediction, not a clinical call.

MYOC p.Ser313Phe

c.938C>T · rs376895063 · VCV2442282

Uncertain significance Expert panel

Classification

Uncertain significance

ClinVar

Review

Expert panel ★★★☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2544 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.029%, eas)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

open-angle glaucoma

ClinGen expert panel

Uncertain Significance — Glaucoma VCEP (open-angle glaucoma).

Computational evidence

Protein change
AlphaMissense	0.2544	likely benign
REVEL	0.554	indeterminate
SaProt	LLR -11.12	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	phastCons 1
Regional constraint	o/e 0.92	unconstrained · MANE · 17 kb · p 0.038 · regional, not allelic
Overall
CADD	25.8	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.029% East Asian · 13/44,872 alleles

Filtering AF 0.0171% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0136%

Overall 0.00093% 15/1,612,748 alleles · ultra-rare exomes 12/1,460,474 · genomes 3/152,274 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.029%	3,452
Remaining individualsnot grpmax-eligible	0.00321%	31,199

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: MYOC
Protein: p.Ser313Phe
Coding: c.938C>T
MANE Select: NM_000261
dbSNP: rs376895063
Type: single nucleotide variant
Location: chr1:171636502 (GRCh38)
Gene constraint: LOEUF 1.343 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 79.40 · 24 PDB
Residue 313: a β-strand; the olfactomedin-like domain

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

Disease context

open-angle glaucoma — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

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-ser313phe (accessed [today's date]).

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