Is MYO7A c.3375+33G>C pathogenic?

MYO7A c.3375+33G>C is classified Benign in MYO7A (ClinVar, Multiple submitters, 4 submitters; last evaluated 2021-07-01). Common (popmax 70.9%, afr) — too common for a highly-penetrant pathogenic allele; Associated with Usher syndrome type 1.

How is Usher syndrome inherited?

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

MYO7A c.3375+33G>C

Q: What condition is associated with MYO7A c.3375+33G>C?

MYO7A c.3375+33G>C is associated with Usher syndrome type 1, autosomal recessive nonsyndromic hearing loss 2, autosomal dominant nonsyndromic hearing loss 11 (ClinVar).

Q: How common is MYO7A c.3375+33G>C in the general population?

MYO7A c.3375+33G>C is common (popmax 70.9%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

rs948972 · VCV255662

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Common

common (popmax 70.9%, 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
Splice region	donor +33	near-intronic (+33 nt from the splice site)
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -3.1	GERP -2.4
Non-coding constraint	Z 3.10	1 kb window · o/e 0.77 · regional · uncalibrated
Overall
CADD	0.128	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 70.9% African / African-American · 51,683/72,922 alleles

Filtering AF 70.4% ClinGen BA1/BS1 input FAF95, joint · FAF99 70.2%

Overall 55.4% 853,862/1,542,458 alleles · common exomes 763,561/1,390,286 · genomes 90,301/152,172 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	70.9%	1
Admixed American	64.8%	2
Finnishnot grpmax-eligible	60.8%	2
European (non-Finnish)	55.8%	2
Remaining individualsnot grpmax-eligible	53%	2
Amishnot grpmax-eligible	49.1%	2
East Asian	46.7%	2
Middle Eastern	42.3%	2
Ashkenazi Jewishnot grpmax-eligible	40.2%	2
South Asian	37.7%	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
Coding: c.3375+33G>C
MANE Select: NM_000260
dbSNP: rs948972
Type: single nucleotide variant
Location: chr11:77183190 (GRCh38)
Gene constraint: LOEUF 0.995 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.73 · 1 PDB

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-c-3375-plus-33g-c (accessed [today's date]).

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