Is MYO7A p.Leu2174= (c.6520T>C) pathogenic?

MYO7A p.Leu2174= (c.6520T>C) is classified Likely benign in MYO7A (ClinVar, Multiple submitters, 3 submitters; last evaluated 2026-01-14). Very rare (popmax 0.00831%, nfe); Associated with Usher syndrome type 1B.

What condition is associated with MYO7A p.Leu2174= (c.6520T>C)?

MYO7A p.Leu2174= (c.6520T>C) is associated with Usher syndrome type 1B (ClinVar).

How common is MYO7A p.Leu2174= (c.6520T>C) in the general population?

MYO7A p.Leu2174= (c.6520T>C) is very rare (popmax 0.00831%, nfe) (gnomAD).

MYO7A p.Leu2174=

c.6520T>C · rs377251326 · VCV754320

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00831%, nfe)

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 0.37	GERP -1.5, phastCons 0.99
Overall
CADD	6.035	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00831% European (non-Finnish) · 98/1,179,880 alleles

Filtering AF 0.00697% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00641%

Overall 0.0062% 100/1,613,926 alleles · very rare exomes 99/1,461,702 · genomes 1/152,224 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00831%	12,040
Admixed American	0.00167%	60,010
Remaining individualsnot grpmax-eligible	0.0016%	62,468

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.Leu2174=
Coding: c.6520T>C
MANE Select: NM_000260
dbSNP: rs377251326
Type: single nucleotide variant
Location: chr11:77213941 (GRCh38)
Gene constraint: LOEUF 0.995 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.73 · 1 PDB
Residue 2174: the ferm 2 domain

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.Leu2174Trp Uncertain significance ★★ ⚠ same residue
MYO7A p.Leu2174Phe Uncertain significance ★ ⚠ same residue
MYO7A p.Leu2174Ser Uncertain significance ★ ⚠ 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

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-leu2174 (accessed [today's date]).

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