Is MYO7A p.Gln1990Arg (c.5969A>G) pathogenic?

MYO7A p.Gln1990Arg (c.5969A>G) is classified Conflicting classifications of pathogenicity in MYO7A (ClinVar, Conflicting submitters, 6 submitters; last evaluated 2026-01-28). AlphaMissense: ambiguous (0.3656); Rare (popmax 0.292%, sas); Associated with Inborn genetic diseases.

What condition is associated with MYO7A p.Gln1990Arg (c.5969A>G)?

MYO7A p.Gln1990Arg (c.5969A>G) is associated with Inborn genetic diseases, Usher syndrome type 1B (ClinVar).

How common is MYO7A p.Gln1990Arg (c.5969A>G) in the general population?

MYO7A p.Gln1990Arg (c.5969A>G) is rare (popmax 0.292%, sas) (gnomAD).

What do computational predictors say about MYO7A p.Gln1990Arg (c.5969A>G)?

AlphaMissense predicts ambiguous (score 0.3656) — an in-silico prediction, not a clinical call.

MYO7A p.Gln1990Arg

c.5969A>G · rs560293591 · VCV751273

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 6 submitters

AlphaMissense

ambiguous

0.3656 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.292%, sas)

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.3656	ambiguous
REVEL	0.749	pathogenic-leaning
SaProt	LLR -6.02	tolerated
⇒ REVEL calls this damaging; SaProt does not; AlphaMissense makes no call.
Splicing
SpliceAI	Δ0.76	acceptor loss, 2 bp away · masked 0 · deltas
Constraint at this position
Conservation	phyloP 11	GERP 1.8, phastCons 1
Regional constraint	o/e 0.95	unconstrained · MANE · 84 kb · p 0.0065 · regional, not allelic
Overall
CADD	23.3	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 0.292% South Asian · 253/86,688 alleles

Filtering AF 0.262% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.251%

Overall 0.0174% 276/1,587,174 alleles · rare exomes 261/1,434,916 · genomes 15/152,258 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.292%	343
Remaining individualsnot grpmax-eligible	0.0341%	2,931
East Asian	0.0023%	43,408
Admixed American	0.00177%	56,350

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.Gln1990Arg
Coding: c.5969A>G
MANE Select: NM_000260
dbSNP: rs560293591
Type: single nucleotide variant
Location: chr11:77208721 (GRCh38)
Gene constraint: LOEUF 0.995 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.73 · 1 PDB
Residue 1990: the ferm 2 domain; a β-strand

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.Gln1990Ter Pathogenic/Likely pathogenic ★★ same residue
MYO7A p.Gln1990Glu 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
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-gln1990arg (accessed [today's date]).

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