Is MYO7A p.Leu618= (c.1854G>A) pathogenic?

MYO7A p.Leu618= (c.1854G>A) is classified Conflicting classifications of pathogenicity in MYO7A (ClinVar, Conflicting submitters, 10 submitters; last evaluated 2026-02-02). Rare (popmax 0.491%, nfe); Associated with Usher syndrome type 1.

What condition is associated with MYO7A p.Leu618= (c.1854G>A)?

MYO7A p.Leu618= (c.1854G>A) is associated with Usher syndrome type 1, autosomal recessive nonsyndromic hearing loss 2, autosomal dominant nonsyndromic hearing loss 11 (ClinVar).

How common is MYO7A p.Leu618= (c.1854G>A) in the general population?

MYO7A p.Leu618= (c.1854G>A) is rare (popmax 0.491%, nfe) (gnomAD).

How is Usher syndrome inherited?

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

MYO7A p.Leu618=

c.1854G>A · rs35429535 · VCV43161

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 10 submitters

gnomAD v4.1

Rare

rare (popmax 0.491%, nfe)

Conditions

Usher syndrome type 1

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 6.5	GERP 0.69, phastCons 1
Overall
CADD	10.45	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.491% European (non-Finnish) · 5,644/1,150,368 alleles

Filtering AF 0.48% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.476%

Overall 0.386% 6,011/1,556,814 alleles · rare exomes 5,608/1,404,472 · genomes 403/152,342 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.491%	204
Remaining individualsnot grpmax-eligible	0.326%	306
Admixed American	0.112%	891
African / African-American	0.0709%	1,411
Finnishnot grpmax-eligible	0.0583%	1,714
Middle Eastern	0.0334%	2,997
South Asian	0.0249%	4,010
Ashkenazi Jewishnot grpmax-eligible	0.00697%	14,347

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: MYO7A
Protein: p.Leu618=
Coding: c.1854G>A
MANE Select: NM_000260
dbSNP: rs35429535
Type: single nucleotide variant
Location: chr11:77172804 (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 1 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: autosomal recessive nonsyndromic hearing loss 2 autosomal dominant nonsyndromic hearing loss 11

For Usher syndrome (Orphanet):

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

Similar variants

MYO7A p.Leu618Arg Pathogenic ★ same residue
MYO7A p.Leu618Pro Uncertain significance ★ ⚠ same residue
MYO7A p.Leu618Val 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

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-leu618 (accessed [today's date]).

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