Is MYO7A p.Arg1190Gln (c.3569G>A) pathogenic?

MYO7A p.Arg1190Gln (c.3569G>A) is classified Uncertain significance in MYO7A (ClinVar, Multiple submitters, 4 submitters; last evaluated 2024-12-17). AlphaMissense: likely pathogenic (0.8818); Very rare (popmax 0.00661%, nfe); Associated with Inborn genetic diseases.

What condition is associated with MYO7A p.Arg1190Gln (c.3569G>A)?

MYO7A p.Arg1190Gln (c.3569G>A) is associated with Inborn genetic diseases (ClinVar).

How common is MYO7A p.Arg1190Gln (c.3569G>A) in the general population?

MYO7A p.Arg1190Gln (c.3569G>A) is very rare (popmax 0.00661%, nfe) (gnomAD).

What do computational predictors say about MYO7A p.Arg1190Gln (c.3569G>A)?

AlphaMissense predicts likely pathogenic (score 0.8818) — an in-silico prediction, not a clinical call.

MYO7A p.Arg1190Gln

c.3569G>A · rs200870793 · VCV1449283

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

AlphaMissense

likely pathogenic

0.8818 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00661%, nfe)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.8818	likely pathogenic
REVEL	0.94	strongly pathogenic-leaning
SaProt	LLR -4.48	tolerated
⇒ AlphaMissense and REVEL call this damaging; SaProt does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 1.8, phastCons 1
Regional constraint	o/e 0.95	unconstrained · MANE · 84 kb · p 0.0065 · regional, not allelic
Overall
CADD	33.0	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 0.00661% European (non-Finnish) · 78/1,179,892 alleles

Filtering AF 0.00538% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00498%

Overall 0.00552% 89/1,613,738 alleles · very rare exomes 85/1,461,570 · genomes 4/152,168 · joint denominator

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	0.00783%	12,779
European (non-Finnish)grpmax	0.00661%	15,127
Remaining individualsnot grpmax-eligible	0.0064%	15,616
Admixed American	0.00167%	60,006
African / African-American	0.00133%	74,922

Finnish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Arg1190Gln
Coding: c.3569G>A
MANE Select: NM_000260
dbSNP: rs200870793
Type: single nucleotide variant
Location: chr11:77189409 (GRCh38)
Gene constraint: LOEUF 0.995 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.73 · 1 PDB
Residue 1190: the myth4 1 domain

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

Similar variants

MYO7A p.Arg1190Trp Uncertain significance ★★ ⚠ same residue
MYO7A p.Arg1190= Likely benign ★★ same residue
MYO7A p.Ser1471Pro Pathogenic/Likely pathogenic ★★ same condition
MYO7A p.Ala1005Thr Uncertain significance ★★ ⚠ same condition
MYO7A p.Ala1203Ser Uncertain significance ★★ ⚠ same condition
MYO7A p.Ala1335Asp Uncertain significance ★★ ⚠ same condition
MYO7A p.Ala1551Val Uncertain significance ★★ ⚠ same condition
MYO7A p.Ala1563Val Uncertain significance ★★ ⚠ 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-arg1190gln (accessed [today's date]).

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