Is MYO7A p.Leu1866= (c.5598C>A) pathogenic?

MYO7A p.Leu1866= (c.5598C>A) is classified Benign/Likely benign in MYO7A (ClinVar, Multiple submitters, 9 submitters; last evaluated 2026-03-01). Rare (popmax 0.402%, amr); Associated with Usher syndrome type 1.

What condition is associated with MYO7A p.Leu1866= (c.5598C>A)?

MYO7A p.Leu1866= (c.5598C>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.Leu1866= (c.5598C>A) in the general population?

MYO7A p.Leu1866= (c.5598C>A) is rare (popmax 0.402%, amr) (gnomAD).

How is Usher syndrome inherited?

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

MYO7A p.Leu1866=

c.5598C>A · rs111033504 · VCV43287

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 9 submitters

gnomAD v4.1

Rare

rare (popmax 0.402%, amr)

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 -12	GERP -2.5
Overall
CADD	0.034	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.402% Admixed American · 241/59,962 alleles

Filtering AF 0.36% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.344%

Overall 0.292% 4,706/1,613,434 alleles · rare exomes 4,394/1,461,102 · genomes 312/152,332 · joint denominator

Ancestry group	Frequency	1 in
Amishnot grpmax-eligible	0.658%	152
Admixed Americangrpmax	0.402%	249
European (non-Finnish)	0.355%	282
Remaining individualsnot grpmax-eligible	0.283%	353
Ashkenazi Jewishnot grpmax-eligible	0.149%	671
Middle Eastern	0.066%	1,514
African / African-American	0.048%	2,084
South Asian	0.0121%	8,264
Finnishnot grpmax-eligible	0.00469%	21,304

Amish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Leu1866=
Coding: c.5598C>A
MANE Select: NM_000260
dbSNP: rs111033504
Type: single nucleotide variant
Location: chr11:77205579 (GRCh38)
Gene constraint: LOEUF 0.995 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.73 · 1 PDB
Residue 1866: the myth4 2 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.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
MYO7A p.Glu968Asp Likely pathogenic ★★★ ⚠ same condition
MYO7A p.Gly2187Asp 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-leu1866 (accessed [today's date]).

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