Is MYO7A p.Arg816His (c.2447G>A) pathogenic?

MYO7A p.Arg816His (c.2447G>A) is classified Conflicting classifications of pathogenicity in MYO7A (ClinVar, Conflicting submitters, 7 submitters; last evaluated 2026-01-28). AlphaMissense: likely benign (0.0976); Rare (popmax 0.936%, afr); Associated with Usher syndrome type 1.

What condition is associated with MYO7A p.Arg816His (c.2447G>A)?

MYO7A p.Arg816His (c.2447G>A) is associated with Usher syndrome type 1, autosomal recessive nonsyndromic hearing loss 2, autosomal dominant nonsyndromic hearing loss 11 (ClinVar).

How common is MYO7A p.Arg816His (c.2447G>A) in the general population?

MYO7A p.Arg816His (c.2447G>A) is rare (popmax 0.936%, 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.Arg816His (c.2447G>A)?

AlphaMissense predicts likely benign (score 0.0976) — an in-silico prediction, not a clinical call.

MYO7A p.Arg816His

c.2447G>A · rs148343670 · VCV43183

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 7 submitters

AlphaMissense

likely benign

0.0976 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.936%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Usher syndrome type 1

Computational evidence

Protein change
AlphaMissense	0.0976	likely benign
REVEL	0.131	moderately benign-leaning
SaProt	LLR -6.68	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.23	GERP -1.6, phastCons 0.002
Regional constraint	o/e 0.95	unconstrained · MANE · 84 kb · p 0.0065 · regional, not allelic
Overall
CADD	14.14	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 0.936% African / African-American · 686/73,302 alleles

Filtering AF 0.878% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.855%

Overall 0.0539% 834/1,547,164 alleles · rare exomes 465/1,394,810 · genomes 369/152,354 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.936%	107
Middle Eastern	0.105%	955
Admixed American	0.0427%	2,341
Remaining individualsnot grpmax-eligible	0.0416%	2,405
European (non-Finnish)	0.00775%	12,904
East Asian	0.00487%	20,547
South Asian	0.00475%	21,041

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.Arg816His
Coding: c.2447G>A
MANE Select: NM_000260
dbSNP: rs148343670
Type: single nucleotide variant
Location: chr11:77179814 (GRCh38)
Gene constraint: LOEUF 0.995 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.73 · 1 PDB
Residue 816: the iq 4 domain

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

Also linked: autosomal recessive nonsyndromic hearing loss 2 autosomal dominant nonsyndromic hearing loss 11 Usher syndrome type 1B

For Usher syndrome (Orphanet):

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

Similar variants

MYO7A p.Arg816Cys Uncertain significance ★★ ⚠ same residue
MYO7A p.Arg816= 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-arg816his (accessed [today's date]).

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