Is MYO7A c.285+1G>C pathogenic?

MYO7A c.285+1G>C is classified Pathogenic/Likely pathogenic in MYO7A (ClinVar, Multiple submitters, 5 submitters; last evaluated 2025-11-10). Very rare (popmax 0.000262%, nfe); Associated with Usher syndrome type 1B.

What condition is associated with MYO7A c.285+1G>C?

MYO7A c.285+1G>C is associated with Usher syndrome type 1B, Usher syndrome type 1, autosomal recessive nonsyndromic hearing loss 2 (ClinVar).

How common is MYO7A c.285+1G>C in the general population?

MYO7A c.285+1G>C is very rare (popmax 0.000262%, nfe) (gnomAD).

MYO7A c.285+1G>C

rs782661097 · VCV419493

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

Consequence

canonical splice-site (±1/±2)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.000262%, nfe)

Conditions

Usher syndrome type 1B

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Consequence	canonical splice-site (±1/±2)	predicted loss-of-function
Splicing
Splice region	donor +1	canonical splice dinucleotide (donor +1) · inside the BP7-excluded zone
SpliceAI	Δ0.99	donor loss · deltas
Pangolin	Δ0.88	loss · gain 0.30 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 9.7	GERP 1.6, phastCons 1
Non-coding constraint	Z 2.38	1 kb window · o/e 0.85 · regional · uncalibrated
Overall
CADD	35.0	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000262% European (non-Finnish) · 3/1,143,194 alleles

Filtering AF 7e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.9e-05%

Overall 0.000194% 3/1,542,702 alleles · very rare exomes 2/1,390,850 · genomes 1/151,852 · joint denominator

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.285+1G>C
MANE Select: NM_000260
dbSNP: rs782661097
Type: single nucleotide variant
Location: chr11:77147951 (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 1B — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: Usher syndrome type 1 autosomal recessive nonsyndromic hearing loss 2 autosomal dominant nonsyndromic hearing loss 11

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-285-plus-1g-c (accessed [today's date]).

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