Is MYO7A p.Ser1530Leu (c.4589C>T) pathogenic?

MYO7A p.Ser1530Leu (c.4589C>T) is classified Benign/Likely benign in MYO7A (ClinVar, Multiple submitters, 11 submitters; last evaluated 2026-02-02). AlphaMissense: likely benign (0.1439); Common (popmax 7.67%, afr) — too common for a highly-penetrant pathogenic allele; Associated with Usher syndrome type 1.

What condition is associated with MYO7A p.Ser1530Leu (c.4589C>T)?

MYO7A p.Ser1530Leu (c.4589C>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.

What do computational predictors say about MYO7A p.Ser1530Leu (c.4589C>T)?

AlphaMissense predicts likely benign (score 0.1439) — an in-silico prediction, not a clinical call.

MYO7A p.Ser1530Leu

Q: How common is MYO7A p.Ser1530Leu (c.4589C>T) in the general population?

MYO7A p.Ser1530Leu (c.4589C>T) is common (popmax 7.67%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.4589C>T · rs111033183 · VCV43248

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 11 submitters

AlphaMissense

likely benign

0.1439 · ACMG-weighted

gnomAD v4.1

Common

common (popmax 7.67%, afr) — too common for a highly-penetrant pathogenic allele

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

Usher syndrome type 1

Computational evidence

Protein change
AlphaMissense	0.1439	likely benign
REVEL	0.326	indeterminate
SaProt	LLR -6.42	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.54	GERP -0.76, phastCons 0.92
Regional constraint	o/e 0.95	unconstrained · MANE · 84 kb · p 0.0065 · regional, not allelic
Overall
CADD	18.95	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 7.67% African / African-American · 5,590/72,868 alleles

Filtering AF 7.5% ClinGen BA1/BS1 input FAF95, joint · FAF99 7.43%

Overall 0.43% 6,524/1,517,142 alleles · common exomes 3,172/1,364,808 · genomes 3,352/152,334 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	7.67%	13
Middle Eastern	0.709%	141
Admixed American	0.701%	143
Remaining individualsnot grpmax-eligible	0.547%	183
European (non-Finnish)	0.019%	5,261
South Asian	0.019%	5,263
Finnishnot grpmax-eligible	0.00517%	19,359

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.Ser1530Leu
Coding: c.4589C>T
MANE Select: NM_000260
dbSNP: rs111033183
Type: single nucleotide variant
Location: chr11:77199555 (GRCh38)
Gene constraint: LOEUF 0.995 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.73 · 1 PDB
Residue 1530: the ferm 1 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.Ser1530= Likely benign ★ 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-ser1530leu (accessed [today's date]).

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