Is MYO7A p.Ile156= (c.468C>T) pathogenic?

MYO7A p.Ile156= (c.468C>T) is classified Benign/Likely benign in MYO7A (ClinVar, Multiple submitters, 13 submitters; last evaluated 2026-02-04). Common (popmax 16%, amr) — too common for a highly-penetrant pathogenic allele; Associated with Usher syndrome type 1.

What condition is associated with MYO7A p.Ile156= (c.468C>T)?

MYO7A p.Ile156= (c.468C>T) is associated with Usher syndrome type 1, autosomal recessive nonsyndromic hearing loss 2, autosomal dominant nonsyndromic hearing loss 11 (ClinVar).

How is Usher syndrome inherited?

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

MYO7A p.Ile156=

Q: How common is MYO7A p.Ile156= (c.468C>T) in the general population?

MYO7A p.Ile156= (c.468C>T) is common (popmax 16%, amr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.468C>T · rs12420129 · VCV43252

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 13 submitters

gnomAD v4.1

Common

common (popmax 16%, amr) — too common for a highly-penetrant pathogenic allele

Conditions

Usher syndrome type 1

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.7	GERP 0.87, phastCons 1
Overall
CADD	18.51	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 16% Admixed American · 9,576/59,918 alleles

Filtering AF 15.7% ClinGen BA1/BS1 input FAF95, joint · FAF99 15.6%

Overall 2.6% 41,878/1,613,478 alleles · common exomes 37,188/1,461,136 · genomes 4,690/152,342 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	16%	6
Finnishnot grpmax-eligible	9.43%	11
Remaining individualsnot grpmax-eligible	2.2%	45
European (non-Finnish)	1.95%	51
South Asian	1.33%	75
Ashkenazi Jewishnot grpmax-eligible	0.753%	133
Middle Eastern	0.742%	135
African / African-American	0.485%	206
Amishnot grpmax-eligible	0.329%	304
East Asian	0.0869%	1,151

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.Ile156=
Coding: c.468C>T
MANE Select: NM_000260
dbSNP: rs12420129
Type: single nucleotide variant
Location: chr11:77156089 (GRCh38)
Gene constraint: LOEUF 0.995 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.73 · 1 PDB
Residue 156: the myosin motor domain

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.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-p-ile156 (accessed [today's date]).

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