Is MYO7A c.*504C>T pathogenic?

MYO7A c.504C>T is classified Benign/Likely benign in MYO7A (ClinVar, Multiple submitters, 3 submitters; last evaluated 2021-05-13). Common (popmax 12.8%, mid) — too common for a highly-penetrant pathogenic allele; Associated with autosomal dominant nonsyndromic hearing loss 11.

What condition is associated with MYO7A c.*504C>T?

MYO7A c.*504C>T is associated with autosomal dominant nonsyndromic hearing loss 11, Usher syndrome type 1, autosomal recessive nonsyndromic hearing loss 2 (ClinVar).

MYO7A c.*504C>T

Q: How common is MYO7A c.*504C>T in the general population?

MYO7A c.*504C>T is common (popmax 12.8%, mid) — too common for a highly-penetrant pathogenic allele (gnomAD).

rs34765389 · VCV306210

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Common

common (popmax 12.8%, mid) — too common for a highly-penetrant pathogenic allele

Conditions

autosomal dominant nonsyndromic hearing loss 11

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 0.11	GERP 0.57
Non-coding constraint	Z -0.16	1 kb window · o/e 1.01 · regional · uncalibrated
Overall
CADD	3.45	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 12.8% Middle Eastern · 42/328 alleles

Filtering AF 11% ClinGen BA1/BS1 input FAF95, joint · FAF99 10.9%

Overall 7.39% 11,854/160,464 alleles · common exomes 835/8,190 · genomes 11,019/152,274 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	12.8%	8
Ashkenazi Jewishnot grpmax-eligible	12.1%	8
European (non-Finnish)	11.2%	9
Amishnot grpmax-eligible	10.6%	9
Remaining individualsnot grpmax-eligible	8.38%	12
Admixed American	7.39%	14
Finnishnot grpmax-eligible	5.36%	19
South Asian	2.82%	35
African / African-American	2.22%	45
East Asian	0.11%	907

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
Coding: c.*504C>T
MANE Select: NM_000260
dbSNP: rs34765389
Type: single nucleotide variant
Location: chr11:77215200 (GRCh38)
Gene constraint: LOEUF 0.995 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.73 · 1 PDB

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

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-c-star-504c-t (accessed [today's date]).

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