Is MYO7A p.Arg2024Pro (c.6071G>C) pathogenic?

MYO7A p.Arg2024Pro (c.6071G>C) is classified Conflicting classifications of pathogenicity in MYO7A (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2025-09-08). AlphaMissense: likely pathogenic (0.9971); Very rare (popmax 0.00355%, amr); Associated with Usher syndrome type 1.

What condition is associated with MYO7A p.Arg2024Pro (c.6071G>C)?

MYO7A p.Arg2024Pro (c.6071G>C) is associated with Usher syndrome type 1 (ClinVar).

How common is MYO7A p.Arg2024Pro (c.6071G>C) in the general population?

MYO7A p.Arg2024Pro (c.6071G>C) is very rare (popmax 0.00355%, amr) (gnomAD).

How is Usher syndrome inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

What do computational predictors say about MYO7A p.Arg2024Pro (c.6071G>C)?

AlphaMissense predicts likely pathogenic (score 0.9971) — an in-silico prediction, not a clinical call.

MYO7A p.Arg2024Pro

c.6071G>C · rs770778096 · VCV1172719

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

AlphaMissense

likely pathogenic

0.9971 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00355%, amr)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Usher syndrome type 1

Computational evidence

Protein change
AlphaMissense	0.9971	likely pathogenic · top 5% in MYO7A
REVEL	0.896	moderately pathogenic-leaning
SaProt	LLR -14.58	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 12	GERP 1.8, phastCons 1
Regional constraint	o/e 0.95	unconstrained · MANE · 84 kb · p 0.0065 · regional, not allelic
Overall
CADD	33.0	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 0.00355% Admixed American · 2/56,314 alleles

Filtering AF 0.000589% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00022%

Overall 0.000126% 2/1,586,244 alleles · very rare exomes 2/1,433,976 · genomes 0/152,268 · joint denominator

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.Arg2024Pro
Coding: c.6071G>C
MANE Select: NM_000260
dbSNP: rs770778096
Type: single nucleotide variant
Location: chr11:77211171 (GRCh38)
Gene constraint: LOEUF 0.995 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.73 · 1 PDB
Residue 2024: 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 1 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Usher syndrome (Orphanet):

Inheritance: Autosomal recessive
Onset: Childhood, Infancy, Neonatal
Prevalence: 1-9 / 100 000 (Worldwide)

Similar variants

MYO7A p.Arg2024Ter Pathogenic ★★ same residue
MYO7A p.Arg2024Gln 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-arg2024pro (accessed [today's date]).

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