Is MYO7A p.Ser2055= (c.6165C>T) pathogenic?

MYO7A p.Ser2055= (c.6165C>T) is classified Conflicting classifications of pathogenicity in MYO7A (ClinVar, Conflicting submitters, 7 submitters; last evaluated 2026-01-21). Ultra-rare (popmax 0.0818%, amr); Associated with Usher syndrome type 1B.

What condition is associated with MYO7A p.Ser2055= (c.6165C>T)?

MYO7A p.Ser2055= (c.6165C>T) is associated with Usher syndrome type 1B (ClinVar).

How common is MYO7A p.Ser2055= (c.6165C>T) in the general population?

MYO7A p.Ser2055= (c.6165C>T) is ultra-rare (popmax 0.0818%, amr) (gnomAD).

MYO7A p.Ser2055=

c.6165C>T · rs397516327 · VCV43319

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 7 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0818%, amr)

Conditions

Usher syndrome type 1B

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 -1.4	GERP -3.5, phastCons 0.001
Overall
CADD	5.235	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0818% Admixed American · 45/55,032 alleles

Filtering AF 0.0628% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.056%

Overall 0.0409% 647/1,580,762 alleles · ultra-rare exomes 604/1,428,586 · genomes 43/152,176 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0818%	1,223
European (non-Finnish)	0.0502%	1,992
Remaining individualsnot grpmax-eligible	0.0212%	4,716
African / African-American	0.00404%	24,750
Finnishnot grpmax-eligible	0.00324%	30,886

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.Ser2055=
Coding: c.6165C>T
MANE Select: NM_000260
dbSNP: rs397516327
Type: single nucleotide variant
Location: chr11:77211265 (GRCh38)
Gene constraint: LOEUF 0.995 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.73 · 1 PDB
Residue 2055: 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 1B — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

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-ser2055 (accessed [today's date]).

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