Is MYO7A p.His1217= (c.3651C>T) pathogenic?

MYO7A p.His1217= (c.3651C>T) is classified Likely benign in MYO7A (ClinVar, Multiple submitters, 6 submitters; last evaluated 2025-09-25). Ultra-rare (popmax 0.0553%, mid); Associated with Usher syndrome type 1B.

What condition is associated with MYO7A p.His1217= (c.3651C>T)?

MYO7A p.His1217= (c.3651C>T) is associated with Usher syndrome type 1B (ClinVar).

How common is MYO7A p.His1217= (c.3651C>T) in the general population?

MYO7A p.His1217= (c.3651C>T) is ultra-rare (popmax 0.0553%, mid) (gnomAD).

MYO7A p.His1217=

c.3651C>T · rs776731918 · VCV760829

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0553%, mid)

Conditions

Usher syndrome type 1B

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>G here scores Δ0.61 · evaluated, not missing
Constraint at this position
Conservation	phyloP -20	GERP -3.3
Overall
CADD	0.208	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0553% Middle Eastern · 3/5,422 alleles

Filtering AF 0.0151% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00962%

Overall 0.00987% 154/1,559,618 alleles · ultra-rare exomes 143/1,407,424 · genomes 11/152,194 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0553%	1,807
European (non-Finnish)	0.0119%	8,412
African / African-American	0.00951%	10,513
Remaining individualsnot grpmax-eligible	0.00828%	12,074
Admixed American	0.00383%	26,081

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.His1217=
Coding: c.3651C>T
MANE Select: NM_000260
dbSNP: rs776731918
Type: single nucleotide variant
Location: chr11:77190040 (GRCh38)
Gene constraint: LOEUF 0.995 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.73 · 1 PDB
Residue 1217: the myth4 1 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

Similar variants

MYO7A p.His1217Gln Uncertain significance ★★ ⚠ 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
MYO7A p.Glu968Asp 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-his1217 (accessed [today's date]).

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