Is MYO7A p.Arg866= (c.2598C>T) pathogenic?

MYO7A p.Arg866= (c.2598C>T) is classified Conflicting classifications of pathogenicity in MYO7A (ClinVar, Conflicting submitters, 5 submitters; last evaluated 2026-01-12). Ultra-rare (popmax 0.0373%, afr); Associated with autosomal recessive nonsyndromic hearing loss 2.

What condition is associated with MYO7A p.Arg866= (c.2598C>T)?

MYO7A p.Arg866= (c.2598C>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.Arg866= (c.2598C>T) in the general population?

MYO7A p.Arg866= (c.2598C>T) is ultra-rare (popmax 0.0373%, afr) (gnomAD).

MYO7A p.Arg866=

c.2598C>T · rs375968860 · VCV883582

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 5 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0373%, afr)

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 -0.61	GERP -3.2, phastCons 0.023
Overall
CADD	4.471	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0373% African / African-American · 28/75,048 alleles

Filtering AF 0.0265% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0229%

Overall 0.00347% 56/1,612,486 alleles · ultra-rare exomes 32/1,460,164 · genomes 24/152,322 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0373%	2,680
Remaining individualsnot grpmax-eligible	0.0064%	15,613
European (non-Finnish)	0.00195%	51,292
Admixed American	0.00167%	59,958

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.Arg866=
Coding: c.2598C>T
MANE Select: NM_000260
dbSNP: rs375968860
Type: single nucleotide variant
Location: chr11:77180385 (GRCh38)
Gene constraint: LOEUF 0.995 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.73 · 1 PDB
Residue 866: the 'sah' region

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

Similar variants

MYO7A p.Arg866His Uncertain significance ★★ ⚠ same residue
MYO7A p.Arg866Cys Uncertain significance ★★ same residue
MYO7A p.Arg866Pro Uncertain significance ★ ⚠ same residue
MYO7A p.Arg866Ser 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

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-arg866 (accessed [today's date]).

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