Is MYO7A p.Leu618Arg (c.1853T>G) pathogenic?

MYO7A p.Leu618Arg (c.1853T>G) is classified Pathogenic in MYO7A (ClinVar, Single submitter, 1 submitter; last evaluated 2020-01-09). AlphaMissense: likely pathogenic (0.9927); Absent from gnomAD v4.1; Associated with Usher syndrome type 2.

What condition is associated with MYO7A p.Leu618Arg (c.1853T>G)?

MYO7A p.Leu618Arg (c.1853T>G) is associated with Usher syndrome type 2 (ClinVar).

How common is MYO7A p.Leu618Arg (c.1853T>G) in the general population?

MYO7A p.Leu618Arg (c.1853T>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.Leu618Arg (c.1853T>G)?

AlphaMissense predicts likely pathogenic (score 0.9927) — an in-silico prediction, not a clinical call.

MYO7A p.Leu618Arg

c.1853T>G · rs1954240719 · VCV813193

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9927 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Usher syndrome type 2

Computational evidence

Protein change
AlphaMissense	0.9927	likely pathogenic ✓ concordant with ClinVar
REVEL	0.975	strongly pathogenic-leaning
SaProt	LLR -14.32	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 7.8	GERP 1.8, phastCons 1
Regional constraint	o/e 0.95	unconstrained · MANE · 84 kb · p 0.0065 · regional, not allelic
Overall
CADD	29.8	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

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.Leu618Arg
Coding: c.1853T>G
MANE Select: NM_000260
dbSNP: rs1954240719
Type: single nucleotide variant
Location: chr11:77172803 (GRCh38)
Gene constraint: LOEUF 0.995 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.73 · 1 PDB
Residue 618: the myosin motor domain

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

Disease context

Usher syndrome type 2 — 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.Leu618= Conflicting classifications of pathogenicity ★ same residue
MYO7A p.Leu618Pro Uncertain significance ★ ⚠ same residue
MYO7A p.Leu618Val Uncertain significance ★ ⚠ same residue
MYO7A p.Arg666Pro Pathogenic ★ same condition
MYO7A p.Trp47fs Pathogenic/Likely pathogenic ★★ same condition
MYO7A p.Ala1288Pro Likely pathogenic ★★★ same type
MYO7A p.Arg1168Gln Pathogenic ★★★ ⚠ same type
MYO7A p.Arg1873Gln Pathogenic ★★★ ⚠ same type

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-leu618arg (accessed [today's date]).

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