Is MYO7A p.Arg1240Trp (c.3718C>T) pathogenic?

MYO7A p.Arg1240Trp (c.3718C>T) is classified Pathogenic/Likely pathogenic in MYO7A (ClinVar, Multiple submitters, 7 submitters; last evaluated 2026-06-30). AlphaMissense: likely pathogenic (0.9994); Very rare (popmax 0.007%, eas); Associated with Usher syndrome type 1B.

What condition is associated with MYO7A p.Arg1240Trp (c.3718C>T)?

MYO7A p.Arg1240Trp (c.3718C>T) is associated with Usher syndrome type 1B, ear malformation, Usher syndrome type 1 (ClinVar).

How common is MYO7A p.Arg1240Trp (c.3718C>T) in the general population?

MYO7A p.Arg1240Trp (c.3718C>T) is very rare (popmax 0.007%, eas) (gnomAD).

What do computational predictors say about MYO7A p.Arg1240Trp (c.3718C>T)?

AlphaMissense predicts likely pathogenic (score 0.9994) — an in-silico prediction, not a clinical call.

MYO7A p.Arg1240Trp

c.3718C>T · rs371374104 · VCV964372

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 7 submitters

AlphaMissense

likely pathogenic

0.9994 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.007%, eas)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Usher syndrome type 1B

Computational evidence

Protein change
AlphaMissense	0.9994	likely pathogenic ✓ concordant with ClinVar · top 1% in MYO7A
REVEL	0.92	moderately pathogenic-leaning
SaProt	LLR -14.72	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 1.7	GERP -0.53, phastCons 0.91
Regional constraint	o/e 0.95	unconstrained · MANE · 84 kb · p 0.0065 · regional, not allelic
Overall
CADD	24.3	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 0.007% East Asian · 3/42,828 alleles

Filtering AF 0.00186% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00101%

Overall 0.000508% 8/1,575,030 alleles · very rare exomes 5/1,422,666 · genomes 3/152,364 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.007%	14,276
African / African-American	0.00135%	74,242
European (non-Finnish)	0.000345%	290,203

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.Arg1240Trp
Coding: c.3718C>T
MANE Select: NM_000260
dbSNP: rs371374104
Type: single nucleotide variant
Location: chr11:77190107 (GRCh38)
Gene constraint: LOEUF 0.995 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.73 · 1 PDB
Residue 1240: the myth4 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

Also linked: ear malformation Usher syndrome type 1 autosomal recessive nonsyndromic hearing loss 2 autosomal dominant nonsyndromic hearing loss 11 Usher syndrome

Similar variants

MYO7A p.Arg1240Gln Pathogenic/Likely pathogenic ★★ same residue
MYO7A p.Arg1240= 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-arg1240trp (accessed [today's date]).

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