Is MYO7A p.Arg1019Trp (c.3055C>T) pathogenic?

MYO7A p.Arg1019Trp (c.3055C>T) is classified Uncertain significance in MYO7A (ClinVar, Single submitter, 1 submitter; last evaluated 2022-04-06). AlphaMissense: likely pathogenic (0.7338); Very rare (popmax 0.00329%, sas).

How common is MYO7A p.Arg1019Trp (c.3055C>T) in the general population?

MYO7A p.Arg1019Trp (c.3055C>T) is very rare (popmax 0.00329%, sas) (gnomAD).

What do computational predictors say about MYO7A p.Arg1019Trp (c.3055C>T)?

AlphaMissense predicts likely pathogenic (score 0.7338) — an in-silico prediction, not a clinical call.

MYO7A p.Arg1019Trp

c.3055C>T · rs781904621 · VCV866774

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7338 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00329%, sas)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.7338	likely pathogenic
REVEL	0.826	moderately pathogenic-leaning
SaProt	LLR -12.45	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 4	GERP 0.7, phastCons 1
Regional constraint	o/e 0.95	unconstrained · MANE · 84 kb · p 0.0065 · regional, not allelic
Overall
CADD	26.5	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 0.00329% South Asian · 3/91,084 alleles

Filtering AF 0.000875% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000443%

Overall 0.000868% 14/1,613,292 alleles · very rare exomes 12/1,461,150 · genomes 2/152,142 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00329%	30,361
East Asian	0.00223%	44,872
Remaining individualsnot grpmax-eligible	0.0016%	62,460
African / African-American	0.00133%	74,912
European (non-Finnish)	0.000678%	147,485

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.Arg1019Trp
Coding: c.3055C>T
MANE Select: NM_000260
dbSNP: rs781904621
Type: single nucleotide variant
Location: chr11:77182101 (GRCh38)
Gene constraint: LOEUF 0.995 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.73 · 1 PDB
Residue 1019: the myth4 1 domain

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

Similar variants

MYO7A p.Arg1019Gln Uncertain significance ★★ same residue
MYO7A p.Ala1288Pro Likely pathogenic ★★★ same type
MYO7A p.Arg1168Gln Pathogenic ★★★ ⚠ same type
MYO7A p.Arg1873Gln Pathogenic ★★★ ⚠ same type
MYO7A p.Arg395Cys Likely pathogenic ★★★ ⚠ same type
MYO7A p.Arg668Cys Pathogenic ★★★ same type
MYO7A p.Arg853His Likely pathogenic ★★★ same type
MYO7A p.Glu968Asp Likely pathogenic ★★★ ⚠ same type

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-arg1019trp (accessed [today's date]).

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