Is MYO7A p.Ser2080= (c.6240C>T) pathogenic?

MYO7A p.Ser2080= (c.6240C>T) is classified Benign/Likely benign in MYO7A (ClinVar, Multiple submitters, 9 submitters; last evaluated 2026-02-04). Low-frequency (popmax 4.74%, mid); Associated with Usher syndrome type 1.

What condition is associated with MYO7A p.Ser2080= (c.6240C>T)?

MYO7A p.Ser2080= (c.6240C>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.Ser2080= (c.6240C>T) in the general population?

MYO7A p.Ser2080= (c.6240C>T) is low-frequency (popmax 4.74%, mid) (gnomAD).

How is Usher syndrome inherited?

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

MYO7A p.Ser2080=

c.6240C>T · rs41298757 · VCV43323

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 9 submitters

gnomAD v4.1

Rare

low-frequency (popmax 4.74%, mid)

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 0.42	GERP -1.8, phastCons 0.99
Overall
CADD	1.218	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 4.74% Middle Eastern · 287/6,058 alleles

Filtering AF 4.29% ClinGen BA1/BS1 input FAF95, joint · FAF99 4.11%

Overall 3.36% 54,274/1,613,416 alleles · low-frequency exomes 50,467/1,461,132 · genomes 3,807/152,284 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	4.74%	21
European (non-Finnish)	4.01%	25
Amishnot grpmax-eligible	3.51%	29
Remaining individualsnot grpmax-eligible	3.03%	33
South Asian	2.11%	47
Ashkenazi Jewishnot grpmax-eligible	1.71%	59
Admixed American	1.53%	66
Finnishnot grpmax-eligible	1.43%	70
African / African-American	0.705%	142
East Asian	0.00892%	11,216

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.Ser2080=
Coding: c.6240C>T
MANE Select: NM_000260
dbSNP: rs41298757
Type: single nucleotide variant
Location: chr11:77211823 (GRCh38)
Gene constraint: LOEUF 0.995 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.73 · 1 PDB
Residue 2080: 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.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-ser2080 (accessed [today's date]).

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