Is MYO7A p.Leu789Pro (c.2366T>C) pathogenic?

MYO7A p.Leu789Pro (c.2366T>C) is classified Uncertain significance in MYO7A (ClinVar, Multiple submitters, 6 submitters; last evaluated 2026-02-01). AlphaMissense: likely pathogenic (0.7443); Ultra-rare (popmax 0.0362%, eas); Associated with Inborn genetic diseases.

What condition is associated with MYO7A p.Leu789Pro (c.2366T>C)?

MYO7A p.Leu789Pro (c.2366T>C) is associated with Inborn genetic diseases, Usher syndrome type 1, autosomal recessive nonsyndromic hearing loss 2 (ClinVar).

How common is MYO7A p.Leu789Pro (c.2366T>C) in the general population?

MYO7A p.Leu789Pro (c.2366T>C) is ultra-rare (popmax 0.0362%, eas) (gnomAD).

What do computational predictors say about MYO7A p.Leu789Pro (c.2366T>C)?

AlphaMissense predicts likely pathogenic (score 0.7443) — an in-silico prediction, not a clinical call.

MYO7A p.Leu789Pro

c.2366T>C · rs751034678 · VCV991222

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

AlphaMissense

likely pathogenic

0.7443 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0362%, eas)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.7443	likely pathogenic
REVEL	0.402	indeterminate
SaProt	LLR -4.81	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5	GERP 1.4, phastCons 1
Regional constraint	o/e 0.95	unconstrained · MANE · 84 kb · p 0.0065 · regional, not allelic
Overall
CADD	22.5	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 0.0362% East Asian · 16/44,250 alleles

Filtering AF 0.0226% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0184%

Overall 0.00169% 27/1,598,288 alleles · ultra-rare exomes 24/1,446,022 · genomes 3/152,266 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0362%	2,766
Admixed American	0.0137%	7,283
Remaining individualsnot grpmax-eligible	0.00161%	61,948
African / African-American	0.00134%	74,668
European (non-Finnish)	8.53e-05%	1,172,961

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.Leu789Pro
Coding: c.2366T>C
MANE Select: NM_000260
dbSNP: rs751034678
Type: single nucleotide variant
Location: chr11:77179128 (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

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: Usher syndrome type 1 autosomal recessive nonsyndromic hearing loss 2 autosomal dominant nonsyndromic hearing loss 11 Usher syndrome type 1B

Similar variants

MYO7A p.Leu789= 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
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-leu789pro (accessed [today's date]).

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