Is MYO7A p.Arg684Trp (c.2050C>T) pathogenic?

MYO7A p.Arg684Trp (c.2050C>T) is classified Uncertain significance in MYO7A (ClinVar, Multiple submitters, 4 submitters; last evaluated 2025-09-09). AlphaMissense: likely pathogenic (0.9642); Ultra-rare (popmax 0.0178%, eas); Associated with Inborn genetic diseases.

What condition is associated with MYO7A p.Arg684Trp (c.2050C>T)?

MYO7A p.Arg684Trp (c.2050C>T) is associated with Inborn genetic diseases, inherited retinal dystrophy (ClinVar).

How common is MYO7A p.Arg684Trp (c.2050C>T) in the general population?

MYO7A p.Arg684Trp (c.2050C>T) is ultra-rare (popmax 0.0178%, eas) (gnomAD).

What do computational predictors say about MYO7A p.Arg684Trp (c.2050C>T)?

AlphaMissense predicts likely pathogenic (score 0.9642) — an in-silico prediction, not a clinical call.

MYO7A p.Arg684Trp

c.2050C>T · VCV3249239

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

AlphaMissense

likely pathogenic

0.9642 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0178%, eas)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.9642	likely pathogenic
REVEL	0.838	moderately pathogenic-leaning
SaProt	LLR -15.44	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 1.1	GERP -0.66, phastCons 1
Regional constraint	o/e 0.95	unconstrained · MANE · 84 kb · p 0.0065 · regional, not allelic
Overall
CADD	32.0	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 0.0178% East Asian · 8/44,894 alleles

Filtering AF 0.00883% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00641%

Overall 0.00217% 35/1,613,574 alleles · ultra-rare exomes 26/1,461,368 · genomes 9/152,206 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0178%	5,612
African / African-American	0.00667%	14,988
Admixed American	0.005%	19,998
Remaining individualsnot grpmax-eligible	0.0016%	62,464
European (non-Finnish)	0.00144%	69,405
South Asian	0.0011%	91,078

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.Arg684Trp
Coding: c.2050C>T
MANE Select: NM_000260
Type: single nucleotide variant
Location: chr11:77174870 (GRCh38)
Gene constraint: LOEUF 0.995 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.73 · 1 PDB
Residue 684: the myosin motor 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

Also linked: inherited retinal dystrophy

Similar variants

MYO7A p.Arg684Gln Uncertain significance ★★ ⚠ same residue
MYO7A p.Arg684= Likely benign ★ same residue
MYO7A p.Ala1288Pro Likely pathogenic ★★★ same condition
MYO7A p.Arg1168Gln Pathogenic ★★★ ⚠ same condition
MYO7A p.Glu968Asp Likely pathogenic ★★★ ⚠ same condition
MYO7A p.Val1372Gly Likely pathogenic ★★★ same condition
MYO7A p.Arg302His Likely benign ★★★ ⚠ same condition
MYO7A c.2283-1G>T 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-arg684trp (accessed [today's date]).

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