Is MYO7A p.Arg1696Gln (c.5087G>A) pathogenic?

MYO7A p.Arg1696Gln (c.5087G>A) is classified Conflicting classifications of pathogenicity in MYO7A (ClinVar, Conflicting submitters, 5 submitters; last evaluated 2026-08-25). AlphaMissense: likely benign (0.0935); Ultra-rare (popmax 0.0417%, afr); Associated with Inborn genetic diseases.

What condition is associated with MYO7A p.Arg1696Gln (c.5087G>A)?

MYO7A p.Arg1696Gln (c.5087G>A) is associated with Inborn genetic diseases, Usher syndrome type 1B (ClinVar).

How common is MYO7A p.Arg1696Gln (c.5087G>A) in the general population?

MYO7A p.Arg1696Gln (c.5087G>A) is ultra-rare (popmax 0.0417%, afr) (gnomAD).

What do computational predictors say about MYO7A p.Arg1696Gln (c.5087G>A)?

AlphaMissense predicts likely benign (score 0.0935) — an in-silico prediction, not a clinical call.

MYO7A p.Arg1696Gln

c.5087G>A · rs368862510 · VCV991575

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 5 submitters

AlphaMissense

likely benign

0.0935 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0417%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0935	likely benign
REVEL	0.139	moderately benign-leaning
SaProt	LLR -6.92	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 12	GERP -0.41, phastCons 1
Regional constraint	o/e 0.95	unconstrained · MANE · 84 kb · p 0.0065 · regional, not allelic
Overall
CADD	24.6	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 0.0417% African / African-American · 31/74,340 alleles

Filtering AF 0.0302% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0262%

Overall 0.00272% 43/1,579,706 alleles · ultra-rare exomes 21/1,427,406 · genomes 22/152,300 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0417%	2,398
Remaining individualsnot grpmax-eligible	0.00817%	12,238
Admixed American	0.00361%	27,722
South Asian	0.00232%	43,028
East Asian	0.00232%	43,162
European (non-Finnish)	0.000172%	581,024

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.Arg1696Gln
Coding: c.5087G>A
MANE Select: NM_000260
dbSNP: rs368862510
Type: single nucleotide variant
Location: chr11:77202343 (GRCh38)
Gene constraint: LOEUF 0.995 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.73 · 1 PDB

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: Usher syndrome type 1B

Similar variants

MYO7A p.Arg1696Trp Uncertain significance ★★ ⚠ same residue
MYO7A p.Arg1696= 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-arg1696gln (accessed [today's date]).

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