Is MYO7A p.Trp2077Ter (c.6230G>A) pathogenic?

MYO7A p.Trp2077Ter (c.6230G>A) is classified Pathogenic/Likely pathogenic in MYO7A (ClinVar, Multiple submitters, 5 submitters; last evaluated 2025-04-23). Very rare (popmax 0.00129%, nfe); Associated with autosomal dominant nonsyndromic hearing loss 11.

What condition is associated with MYO7A p.Trp2077Ter (c.6230G>A)?

MYO7A p.Trp2077Ter (c.6230G>A) is associated with autosomal dominant nonsyndromic hearing loss 11, Usher syndrome type 1, autosomal recessive nonsyndromic hearing loss 2 (ClinVar).

How common is MYO7A p.Trp2077Ter (c.6230G>A) in the general population?

MYO7A p.Trp2077Ter (c.6230G>A) is very rare (popmax 0.00129%, nfe) (gnomAD).

MYO7A p.Trp2077Ter

c.6230G>A · rs776930594 · VCV620345

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00129%, nfe)

Conditions

autosomal dominant nonsyndromic hearing loss 11

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function
NMD	predicted	premature termination codon in exon 45 of 49
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 1.8, phastCons 1
Overall
CADD	53.0	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 0.00129% European (non-Finnish) · 15/1,162,562 alleles

Filtering AF 0.000775% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000614%

Overall 0.00095% 15/1,578,884 alleles · very rare exomes 15/1,426,576 · genomes 0/152,308 · 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
Protein: p.Trp2077Ter
Coding: c.6230G>A
MANE Select: NM_000260
dbSNP: rs776930594
Type: single nucleotide variant
Location: chr11:77211330 (GRCh38)
Gene constraint: LOEUF 0.995 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.73 · 1 PDB
Residue 2077: the ferm 2 domain; an α-helix

Full MYO7A gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

autosomal dominant nonsyndromic hearing loss 11 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

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

Similar variants

MYO7A p.Trp2077fs Pathogenic ★ same residue
MYO7A p.Trp2077Cys Likely pathogenic ★ 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

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-trp2077ter (accessed [today's date]).

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