Is MYO7A p.Arg825= (c.2475C>T) pathogenic?

MYO7A p.Arg825= (c.2475C>T) is classified Conflicting classifications of pathogenicity in MYO7A (ClinVar, Conflicting submitters, 6 submitters; last evaluated 2026-01-28). Ultra-rare (popmax 0.0784%, amr); Associated with autosomal recessive nonsyndromic hearing loss 2.

What condition is associated with MYO7A p.Arg825= (c.2475C>T)?

MYO7A p.Arg825= (c.2475C>T) is associated with autosomal recessive nonsyndromic hearing loss 2, Usher syndrome type 1, autosomal dominant nonsyndromic hearing loss 11 (ClinVar).

How common is MYO7A p.Arg825= (c.2475C>T) in the general population?

MYO7A p.Arg825= (c.2475C>T) is ultra-rare (popmax 0.0784%, amr) (gnomAD).

MYO7A p.Arg825=

c.2475C>T · rs782711428 · VCV788602

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 6 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0784%, amr)

Conditions

autosomal recessive nonsyndromic hearing loss 2

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -13	GERP -3.5
Overall
CADD	0.892	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0784% Admixed American · 40/51,042 alleles

Filtering AF 0.0591% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0524%

Overall 0.0146% 225/1,542,874 alleles · ultra-rare exomes 207/1,390,614 · genomes 18/152,260 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0784%	1,276
South Asian	0.0357%	2,801
Remaining individualsnot grpmax-eligible	0.0183%	5,453
East Asian	0.0122%	8,190
European (non-Finnish)	0.0118%	8,496
African / African-American	0.00411%	24,353
Finnishnot grpmax-eligible	0.00193%	51,748

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.Arg825=
Coding: c.2475C>T
MANE Select: NM_000260
dbSNP: rs782711428
Type: single nucleotide variant
Location: chr11:77179842 (GRCh38)
Gene constraint: LOEUF 0.995 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.73 · 1 PDB
Residue 825: the iq 4 domain

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

Disease context

autosomal recessive nonsyndromic hearing loss 2 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

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

Similar variants

MYO7A p.Arg825Cys Uncertain significance ★★ ⚠ same residue
MYO7A p.Arg825His Uncertain significance ★★ ⚠ same residue
MYO7A p.Arg825Gly 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

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-arg825 (accessed [today's date]).

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