Is MYO7A p.His1853= (c.5559C>T) pathogenic?

MYO7A p.His1853= (c.5559C>T) is classified Benign/Likely benign in MYO7A (ClinVar, Multiple submitters, 7 submitters; last evaluated 2026-01-24). Ultra-rare (popmax 0.0495%, mid); Associated with Usher syndrome type 1.

What condition is associated with MYO7A p.His1853= (c.5559C>T)?

MYO7A p.His1853= (c.5559C>T) is associated with Usher syndrome type 1, autosomal recessive nonsyndromic hearing loss 2 (ClinVar).

How common is MYO7A p.His1853= (c.5559C>T) in the general population?

MYO7A p.His1853= (c.5559C>T) is ultra-rare (popmax 0.0495%, mid) (gnomAD).

How is Usher syndrome inherited?

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

MYO7A p.His1853=

c.5559C>T · rs373612656 · VCV43286

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 7 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0495%, mid)

Conditions

Usher syndrome type 1

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>G here scores Δ0.94 · evaluated, not missing
Constraint at this position
Conservation	phyloP -9.4	GERP -2.5
Overall
CADD	7.502	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0495% Middle Eastern · 3/6,058 alleles

Filtering AF 0.0364% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0352%

Overall 0.0406% 653/1,610,292 alleles · ultra-rare exomes 583/1,457,962 · genomes 70/152,330 · joint denominator

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	0.248%	403
Middle Easterngrpmax	0.0495%	2,019
European (non-Finnish)	0.0394%	2,540
Remaining individualsnot grpmax-eligible	0.0273%	3,667
African / African-American	0.00667%	14,992
Ashkenazi Jewishnot grpmax-eligible	0.0034%	29,400
Admixed American	0.00335%	29,807
East Asian	0.00223%	44,772
South Asian	0.00223%	44,936

Finnish 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.His1853=
Coding: c.5559C>T
MANE Select: NM_000260
dbSNP: rs373612656
Type: single nucleotide variant
Location: chr11:77205540 (GRCh38)
Gene constraint: LOEUF 0.995 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.73 · 1 PDB
Residue 1853: the myth4 2 domain; an α-helix

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

For Usher syndrome (Orphanet):

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

Similar variants

MYO7A p.His1853Asn Uncertain significance ★ ⚠ same residue
MYO7A p.His1853Asp Uncertain significance ★ ⚠ same residue
MYO7A p.His1853Gln 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-his1853 (accessed [today's date]).

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