Is MYO7A p.Leu1087Arg (c.3260T>G) pathogenic?

MYO7A p.Leu1087Arg (c.3260T>G) is classified Uncertain significance in MYO7A (ClinVar, No assertion criteria, 1 submitter; last evaluated 2020-08-13). AlphaMissense: ambiguous (0.542); Very rare (popmax 0.00223%, eas); Associated with Usher syndrome type 1B.

What condition is associated with MYO7A p.Leu1087Arg (c.3260T>G)?

MYO7A p.Leu1087Arg (c.3260T>G) is associated with Usher syndrome type 1B (ClinVar).

How common is MYO7A p.Leu1087Arg (c.3260T>G) in the general population?

MYO7A p.Leu1087Arg (c.3260T>G) is very rare (popmax 0.00223%, eas) (gnomAD).

What do computational predictors say about MYO7A p.Leu1087Arg (c.3260T>G)?

AlphaMissense predicts ambiguous (score 0.542) — an in-silico prediction, not a clinical call.

MYO7A p.Leu1087Arg

c.3260T>G · rs375050157 · VCV991232

Uncertain significance No assertion criteria

Classification

Uncertain significance

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.542 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00223%, eas)

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense indeterminate

Conditions

Usher syndrome type 1B

Computational evidence

Protein change
AlphaMissense	0.542	ambiguous
REVEL	0.698	pathogenic-leaning
SaProt	LLR -7.75	tolerated
⇒ REVEL calls this damaging; SaProt does not; AlphaMissense is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.8	GERP 1.8, phastCons 1
Regional constraint	o/e 0.95	unconstrained · MANE · 84 kb · p 0.0065 · regional, not allelic
Overall
CADD	24.4	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 0.00223% East Asian · 1/44,876 alleles

Overall 0.000186% 3/1,613,074 alleles · very rare exomes 3/1,460,770 · genomes 0/152,304 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00223%	44,876
Remaining individualsnot grpmax-eligible	0.0016%	62,466
European (non-Finnish)	8.48e-05%	1,179,834

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.Leu1087Arg
Coding: c.3260T>G
MANE Select: NM_000260
dbSNP: rs375050157
Type: single nucleotide variant
Location: chr11:77182575 (GRCh38)
Gene constraint: LOEUF 0.995 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.73 · 1 PDB
Residue 1087: the myth4 1 domain; a UniProt-annotated variant site (in ush1b)

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.Leu1087Gln Uncertain significance ★★ ⚠ same residue
MYO7A p.Leu1087= 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

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-leu1087arg (accessed [today's date]).

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