Is MYO7A p.Met946Arg (c.2837T>G) pathogenic?

MYO7A p.Met946Arg (c.2837T>G) is classified Pathogenic/Likely pathogenic in MYO7A (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-01-29). AlphaMissense: likely pathogenic (0.9524); Absent from gnomAD v4.1; Associated with Usher syndrome type 1.

What condition is associated with MYO7A p.Met946Arg (c.2837T>G)?

MYO7A p.Met946Arg (c.2837T>G) is associated with Usher syndrome type 1 (ClinVar).

How common is MYO7A p.Met946Arg (c.2837T>G) in the general population?

MYO7A p.Met946Arg (c.2837T>G) is absent from gnomAD v4.1 (gnomAD).

How is Usher syndrome inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

What do computational predictors say about MYO7A p.Met946Arg (c.2837T>G)?

AlphaMissense predicts likely pathogenic (score 0.9524) — an in-silico prediction, not a clinical call.

MYO7A p.Met946Arg

c.2837T>G · rs1296612982 · VCV813430

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.9524 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Usher syndrome type 1

Computational evidence

Protein change
AlphaMissense	0.9524	likely pathogenic ✓ concordant with ClinVar
REVEL	0.939	strongly pathogenic-leaning
SaProt	LLR -6.73	tolerated
⇒ AlphaMissense and REVEL call this damaging; SaProt does not.
Splicing
SpliceAI	Δ0.96	donor gain · deltas
Pangolin	Δ0.75	gain · loss 0.00 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 7.9	GERP 1.8, phastCons 1
Regional constraint	o/e 0.95	unconstrained · MANE · 84 kb · p 0.0065 · regional, not allelic
Overall
CADD	35.0	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

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: MYO7A
Protein: p.Met946Arg
Coding: c.2837T>G
MANE Select: NM_000260
dbSNP: rs1296612982
Type: single nucleotide variant
Location: chr11:77181522 (GRCh38)
Gene constraint: LOEUF 0.995 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.73 · 1 PDB
Residue 946: a UniProt-annotated variant site (in ush1b)

Full MYO7A gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Usher syndrome type 1 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Usher syndrome (Orphanet):

Inheritance: Autosomal recessive
Onset: Childhood, Infancy, Neonatal
Prevalence: 1-9 / 100 000 (Worldwide)

Similar variants

MYO7A p.Met946Leu Uncertain significance ★★ ⚠ same residue
MYO7A p.Met946Lys Uncertain significance ★ ⚠ same residue
MYO7A p.Ala1288Pro Likely pathogenic ★★★ same condition
MYO7A p.Arg1168Gln Pathogenic ★★★ ⚠ same condition
MYO7A p.Arg1873Gln Pathogenic ★★★ ⚠ same condition
MYO7A p.Arg395Cys Likely pathogenic ★★★ ⚠ same condition
MYO7A p.Arg668Cys Pathogenic ★★★ same condition
MYO7A p.Arg853His 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/myo7a-p-met946arg (accessed [today's date]).

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