Is MYO7A p.Lys1905= (c.5715A>G) pathogenic?

MYO7A p.Lys1905= (c.5715A>G) is classified Benign in MYO7A (ClinVar, Multiple submitters, 12 submitters; last evaluated 2026-02-04). Common (popmax 70.5%, afr) — too common for a highly-penetrant pathogenic allele; Associated with Usher syndrome type 1.

What condition is associated with MYO7A p.Lys1905= (c.5715A>G)?

MYO7A p.Lys1905= (c.5715A>G) is associated with Usher syndrome type 1, autosomal recessive nonsyndromic hearing loss 2, autosomal dominant nonsyndromic hearing loss 11 (ClinVar).

How is Usher syndrome inherited?

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

MYO7A p.Lys1905=

Q: How common is MYO7A p.Lys1905= (c.5715A>G) in the general population?

MYO7A p.Lys1905= (c.5715A>G) is common (popmax 70.5%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.5715A>G · rs2276293 · VCV43296

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 12 submitters

gnomAD v4.1

Common

common (popmax 70.5%, afr) — too common for a highly-penetrant pathogenic allele

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 2.2	GERP -2.1, phastCons 1
Overall
CADD	6.723	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 70.5% African / African-American · 52,785/74,876 alleles

Filtering AF 70% ClinGen BA1/BS1 input FAF95, joint · FAF99 69.8%

Overall 49.4% 796,316/1,611,312 alleles · common exomes 711,550/1,459,398 · genomes 84,766/151,914 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	70.5%	1
Admixed American	62.2%	2
Finnishnot grpmax-eligible	59.5%	2
Amishnot grpmax-eligible	49.2%	2
East Asian	48.4%	2
Remaining individualsnot grpmax-eligible	48.4%	2
European (non-Finnish)	47.9%	2
Middle Eastern	44.5%	2
Ashkenazi Jewishnot grpmax-eligible	42.2%	2
South Asian	39.5%	3

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.Lys1905=
Coding: c.5715A>G
MANE Select: NM_000260
dbSNP: rs2276293
Type: single nucleotide variant
Location: chr11:77206175 (GRCh38)
Gene constraint: LOEUF 0.995 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.73 · 1 PDB
Residue 1905: the ferm 2 domain; a β-strand

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 Usher syndrome type 1B

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-lys1905 (accessed [today's date]).

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