Is MYO7A p.His1968= (c.5904C>T) pathogenic?

MYO7A p.His1968= (c.5904C>T) is classified Conflicting classifications of pathogenicity in MYO7A (ClinVar, Conflicting submitters, 9 submitters; last evaluated 2026-02-01). Rare (popmax 0.213%, sas); Associated with Usher syndrome type 1.

What condition is associated with MYO7A p.His1968= (c.5904C>T)?

MYO7A p.His1968= (c.5904C>T) is associated with Usher syndrome type 1, autosomal recessive nonsyndromic hearing loss 2, autosomal dominant nonsyndromic hearing loss 11 (ClinVar).

How common is MYO7A p.His1968= (c.5904C>T) in the general population?

MYO7A p.His1968= (c.5904C>T) is rare (popmax 0.213%, sas) (gnomAD).

How is Usher syndrome inherited?

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

MYO7A p.His1968=

c.5904C>T · rs41298753 · VCV43309

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 9 submitters

gnomAD v4.1

Rare

rare (popmax 0.213%, sas)

Conditions

Usher syndrome type 1

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 Δ0.97 · evaluated, not missing
Constraint at this position
Conservation	phyloP -0.5	GERP -1.8, phastCons 0.019
Overall
CADD	7.271	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.213% South Asian · 194/91,016 alleles

Filtering AF 0.189% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.179%

Overall 0.0942% 1,520/1,613,852 alleles · rare exomes 1,410/1,461,508 · genomes 110/152,344 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.213%	469
European (non-Finnish)	0.0992%	1,008
Remaining individualsnot grpmax-eligible	0.096%	1,041
Ashkenazi Jewishnot grpmax-eligible	0.0946%	1,057
Middle Eastern	0.0825%	1,212
Finnishnot grpmax-eligible	0.0625%	1,600
Admixed American	0.0233%	4,287
African / African-American	0.012%	8,340

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.His1968=
Coding: c.5904C>T
MANE Select: NM_000260
dbSNP: rs41298753
Type: single nucleotide variant
Location: chr11:77208477 (GRCh38)
Gene constraint: LOEUF 0.995 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.73 · 1 PDB
Residue 1968: the ferm 2 domain; an α-helix

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 Usher syndrome type 1B

For Usher syndrome (Orphanet):

Inheritance: Autosomal recessive
Onset: Childhood, Infancy, Neonatal
Prevalence: 1-9 / 100 000 (Worldwide)

Similar variants

MYO7A p.His1968Arg 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-his1968 (accessed [today's date]).

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