Is MYO7A p.Asp1981= (c.5943C>T) pathogenic?

MYO7A p.Asp1981= (c.5943C>T) is classified Uncertain significance in MYO7A (ClinVar, Multiple submitters, 3 submitters; last evaluated 2024-12-19). Ultra-rare (popmax 0.0165%, sas); Associated with Usher syndrome type 1.

What condition is associated with MYO7A p.Asp1981= (c.5943C>T)?

MYO7A p.Asp1981= (c.5943C>T) 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.Asp1981= (c.5943C>T) in the general population?

MYO7A p.Asp1981= (c.5943C>T) is ultra-rare (popmax 0.0165%, sas) (gnomAD).

How is Usher syndrome inherited?

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

MYO7A p.Asp1981=

c.5943C>T · rs773907543 · VCV880933

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0165%, sas)

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 Δ0.21 · evaluated, not missing
Constraint at this position
Conservation	phyloP -3.7	GERP -3.2
Overall
CADD	5.302	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0165% South Asian · 15/90,720 alleles

Filtering AF 0.0101% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00824%

Overall 0.00304% 49/1,612,074 alleles · ultra-rare exomes 44/1,459,904 · genomes 5/152,170 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0165%	6,048
Middle Eastern	0.0164%	6,080
East Asian	0.00669%	14,948
African / African-American	0.00267%	37,451
European (non-Finnish)	0.00229%	43,668
Remaining individualsnot grpmax-eligible	0.0016%	62,422

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.Asp1981=
Coding: c.5943C>T
MANE Select: NM_000260
dbSNP: rs773907543
Type: single nucleotide variant
Location: chr11:77208516 (GRCh38)
Gene constraint: LOEUF 0.995 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.73 · 1 PDB
Residue 1981: the ferm 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.Asp1981Gly 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
MYO7A p.Glu968Asp 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-asp1981 (accessed [today's date]).

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