Is MYO7A p.His2027del (c.6079_6081del) pathogenic?

MYO7A p.His2027del (c.60796081del) is classified Conflicting classifications of pathogenicity in MYO7A (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2025-03-03). Very rare (popmax 0.00176%, amr); Associated with Usher syndrome type 1B.

What condition is associated with MYO7A p.His2027del (c.6079_6081del)?

MYO7A p.His2027del (c.6079_6081del) is associated with Usher syndrome type 1B, Usher syndrome type 1, autosomal recessive nonsyndromic hearing loss 2 (ClinVar).

How common is MYO7A p.His2027del (c.6079_6081del) in the general population?

MYO7A p.His2027del (c.6079_6081del) is very rare (popmax 0.00176%, amr) (gnomAD).

MYO7A p.His2027del

c.6079_6081del · rs1957839812 · VCV1406933

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00176%, amr)

Conditions

Usher syndrome type 1B

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 7.9	GERP 1.8, phastCons 1

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00176% Admixed American · 1/56,738 alleles

Overall 0.000126% 2/1,589,934 alleles · very rare exomes 2/1,437,638 · genomes 0/152,296 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00176%	56,738
Remaining individualsnot grpmax-eligible	0.00162%	61,606

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.His2027del
Coding: c.6079_6081del
MANE Select: NM_000260
dbSNP: rs1957839812
Type: Deletion
Location: chr11:77211177 (GRCh38)
Gene constraint: LOEUF 0.995 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.73 · 1 PDB
Residue 2027: the ferm 2 domain

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 c.3503+12_3503+33del Benign ★★★ same condition
MYO7A c.2187+2_2187+8del Pathogenic/Likely pathogenic ★★ same condition
MYO7A c.2283-2_2293del Pathogenic/Likely pathogenic ★★ same condition
MYO7A c.5471_5480+5del Pathogenic/Likely pathogenic ★★ same condition
MYO7A p.Ala1277fs Pathogenic/Likely pathogenic ★★ same condition
MYO7A p.Ala2009fs Pathogenic ★★ same condition
MYO7A p.Ala202fs Pathogenic/Likely pathogenic ★★ same condition
MYO7A p.Ala353_Thr354insTer Pathogenic/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-his2027del (accessed [today's date]).

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