Is MYO7A p.Arg756Gln (c.2267G>A) pathogenic?

MYO7A p.Arg756Gln (c.2267G>A) is classified Uncertain significance in MYO7A (ClinVar, Single submitter, 2 submitters; last evaluated 2025-10-15). AlphaMissense: likely pathogenic (0.6799); Very rare (popmax 0.0067%, amr); Associated with Usher syndrome type 1B.

What condition is associated with MYO7A p.Arg756Gln (c.2267G>A)?

MYO7A p.Arg756Gln (c.2267G>A) is associated with Usher syndrome type 1B (ClinVar).

How common is MYO7A p.Arg756Gln (c.2267G>A) in the general population?

MYO7A p.Arg756Gln (c.2267G>A) is very rare (popmax 0.0067%, amr) (gnomAD).

What do computational predictors say about MYO7A p.Arg756Gln (c.2267G>A)?

AlphaMissense predicts likely pathogenic (score 0.6799) — an in-silico prediction, not a clinical call.

MYO7A p.Arg756Gln

c.2267G>A · rs782719957 · VCV838012

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.6799 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0067%, amr)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Usher syndrome type 1B

Computational evidence

Protein change
AlphaMissense	0.6799	likely pathogenic
REVEL	0.928	moderately pathogenic-leaning
SaProt	LLR -11.47	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 1.6, phastCons 1
Regional constraint	o/e 0.95	unconstrained · MANE · 84 kb · p 0.0065 · regional, not allelic
Overall
CADD	27.3	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0067% Admixed American · 4/59,692 alleles

Filtering AF 0.00226% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00135%

Overall 0.00137% 22/1,610,002 alleles · very rare exomes 17/1,457,886 · genomes 5/152,116 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0067%	14,923
African / African-American	0.00401%	24,941
East Asian	0.00223%	44,816
Finnishnot grpmax-eligible	0.00158%	63,398
European (non-Finnish)	0.0011%	90,654

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.Arg756Gln
Coding: c.2267G>A
MANE Select: NM_000260
dbSNP: rs782719957
Type: single nucleotide variant
Location: chr11:77177628 (GRCh38)
Gene constraint: LOEUF 0.995 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.73 · 1 PDB
Residue 756: the iq 1 domain; a UniProt-annotated variant site (in ush1b)

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

Disease context

Usher syndrome type 1B — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

MYO7A p.Arg756Trp Uncertain significance ★★ ⚠ same residue
MYO7A p.Arg756= 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-arg756gln (accessed [today's date]).

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