Is MYO7A p.Arg616Leu (c.1847G>T) pathogenic?

MYO7A p.Arg616Leu (c.1847G>T) is classified Uncertain significance in MYO7A (ClinVar, No assertion criteria, 1 submitter; last evaluated 2025-02-10). AlphaMissense: likely pathogenic (0.7409); No allele count reported in gnomAD v4.1 (AN 1,558,604); Associated with Usher syndrome type 1B.

What condition is associated with MYO7A p.Arg616Leu (c.1847G>T)?

MYO7A p.Arg616Leu (c.1847G>T) is associated with Usher syndrome type 1B (ClinVar).

How common is MYO7A p.Arg616Leu (c.1847G>T) in the general population?

MYO7A p.Arg616Leu (c.1847G>T) is no allele count reported in gnomAD v4.1 (AN 1,558,604) (gnomAD).

What do computational predictors say about MYO7A p.Arg616Leu (c.1847G>T)?

AlphaMissense predicts likely pathogenic (score 0.7409) — an in-silico prediction, not a clinical call.

MYO7A p.Arg616Leu

c.1847G>T · VCV4058209

Uncertain significance No assertion criteria

Classification

Uncertain significance

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7409 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,558,604)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Usher syndrome type 1B

Computational evidence

Protein change
AlphaMissense	0.7409	likely pathogenic
REVEL	0.737	pathogenic-leaning
SaProt	LLR -5.85	tolerated
⇒ AlphaMissense and REVEL call this damaging; SaProt does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.2	GERP -0.43, phastCons 1
Regional constraint	o/e 0.95	unconstrained · MANE · 84 kb · p 0.0065 · regional, not allelic
Overall
CADD	25.8	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

No allele count reported in gnomAD v4.1 (AN 1,558,604). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: MYO7A
Protein: p.Arg616Leu
Coding: c.1847G>T
MANE Select: NM_000260
Type: single nucleotide variant
Location: chr11:77172797 (GRCh38)
Gene constraint: LOEUF 0.995 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.73 · 1 PDB
Residue 616: the myosin motor 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.Arg616Trp Uncertain significance ★★ ⚠ same residue
MYO7A p.Arg616Gln Conflicting classifications of pathogenicity ★ same residue
MYO7A p.Arg616= 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

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-arg616leu (accessed [today's date]).

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