Is MYO7A p.Arg848Trp (c.2542C>T) pathogenic?

MYO7A p.Arg848Trp (c.2542C>T) is classified Conflicting classifications of pathogenicity in MYO7A (ClinVar, Conflicting submitters, 4 submitters; last evaluated 2026-06-16). AlphaMissense: likely pathogenic (0.6941); Ultra-rare (popmax 0.0219%, afr); Associated with Usher syndrome.

What condition is associated with MYO7A p.Arg848Trp (c.2542C>T)?

MYO7A p.Arg848Trp (c.2542C>T) is associated with Usher syndrome (ClinVar).

How common is MYO7A p.Arg848Trp (c.2542C>T) in the general population?

MYO7A p.Arg848Trp (c.2542C>T) is ultra-rare (popmax 0.0219%, afr) (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.Arg848Trp (c.2542C>T)?

AlphaMissense predicts likely pathogenic (score 0.6941) — an in-silico prediction, not a clinical call.

MYO7A p.Arg848Trp

c.2542C>T · rs1426313451 · VCV2150510

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 4 submitters

AlphaMissense

likely pathogenic

0.6941 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0219%, afr)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Usher syndrome

Computational evidence

Protein change
AlphaMissense	0.6941	likely pathogenic
REVEL	0.84	moderately pathogenic-leaning
SaProt	LLR -12.62	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.6	GERP -3.5, phastCons 0.12
Regional constraint	o/e 0.95	unconstrained · MANE · 84 kb · p 0.0065 · regional, not allelic
Overall
CADD	24.8	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

Grpmax group 0.0219% African / African-American · 16/72,952 alleles

Filtering AF 0.0137% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0112%

Overall 0.00208% 32/1,536,920 alleles · ultra-rare exomes 22/1,384,674 · genomes 10/152,246 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0219%	4,560
Admixed American	0.00393%	25,454
South Asian	0.00238%	41,955
European (non-Finnish)	0.00105%	95,408

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.Arg848Trp
Coding: c.2542C>T
MANE Select: NM_000260
dbSNP: rs1426313451
Type: single nucleotide variant
Location: chr11:77179909 (GRCh38)
Gene constraint: LOEUF 0.995 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.73 · 1 PDB
Residue 848: the iq 5 domain

Full MYO7A gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Usher syndrome — 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.Arg848Gln Uncertain significance ★★ ⚠ same residue
MYO7A p.Arg848Gly 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.Arg668Cys Pathogenic ★★★ same condition
MYO7A p.Gly2187Asp Likely pathogenic ★★★ same condition
MYO7A p.His133Asn 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-arg848trp (accessed [today's date]).

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