Is MYO7A p.Arg467Trp (c.1399C>T) pathogenic?

MYO7A p.Arg467Trp (c.1399C>T) is classified Uncertain significance in MYO7A (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-11-19). AlphaMissense: ambiguous (0.4181); Very rare (popmax 0.00453%, sas); Associated with hearing loss disorder.

What condition is associated with MYO7A p.Arg467Trp (c.1399C>T)?

MYO7A p.Arg467Trp (c.1399C>T) is associated with hearing loss disorder (ClinVar).

How common is MYO7A p.Arg467Trp (c.1399C>T) in the general population?

MYO7A p.Arg467Trp (c.1399C>T) is very rare (popmax 0.00453%, sas) (gnomAD).

What do computational predictors say about MYO7A p.Arg467Trp (c.1399C>T)?

AlphaMissense predicts ambiguous (score 0.4181) — an in-silico prediction, not a clinical call.

MYO7A p.Arg467Trp

c.1399C>T · rs782073796 · VCV1065042

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

ambiguous

0.4181 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00453%, sas)

Conditions

hearing loss disorder

Computational evidence

Protein change
AlphaMissense	0.4181	ambiguous
REVEL	0.37	indeterminate
SaProt	LLR -10.49	damaging
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.18	GERP -1.7, phastCons 0.21
Regional constraint	o/e 0.95	unconstrained · MANE · 84 kb · p 0.0065 · regional, not allelic
Overall
CADD	22.5	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 0.00453% South Asian · 4/88,222 alleles

Filtering AF 0.00146% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000913%

Overall 0.00112% 18/1,602,080 alleles · very rare exomes 14/1,449,932 · genomes 4/152,148 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00453%	22,055
African / African-American	0.00268%	37,375
Admixed American	0.00171%	58,474
Remaining individualsnot grpmax-eligible	0.00161%	62,094
European (non-Finnish)	0.000852%	117,434

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.Arg467Trp
Coding: c.1399C>T
MANE Select: NM_000260
dbSNP: rs782073796
Type: single nucleotide variant
Location: chr11:77162175 (GRCh38)
Gene constraint: LOEUF 0.995 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.73 · 1 PDB
Residue 467: the myosin motor domain

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

Disease context

hearing loss disorder — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

MYO7A p.Arg467Gln Uncertain significance ★★ ⚠ same residue
MYO7A p.Arg467Pro Uncertain significance ★ ⚠ same residue
MYO7A c.4442-1G>C Pathogenic/Likely pathogenic ★★ same condition
MYO7A p.Ala1005Val Uncertain significance ★★ ⚠ same condition
MYO7A p.Ala598Thr Uncertain significance ★★ same condition
MYO7A p.Ala889Val Uncertain significance ★★ ⚠ same condition
MYO7A p.Arg1967Gln Uncertain significance ★★ ⚠ same condition
MYO7A p.Arg796Trp 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-arg467trp (accessed [today's date]).

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