Is MYO7A p.Arg606Leu (c.1817G>T) pathogenic?

MYO7A p.Arg606Leu (c.1817G>T) is classified Uncertain significance in MYO7A (ClinVar, Single submitter, 1 submitter; last evaluated 2022-05-05). AlphaMissense: likely pathogenic (0.9495); Very rare (popmax 0.000347%, nfe).

How common is MYO7A p.Arg606Leu (c.1817G>T) in the general population?

MYO7A p.Arg606Leu (c.1817G>T) is very rare (popmax 0.000347%, nfe) (gnomAD).

What do computational predictors say about MYO7A p.Arg606Leu (c.1817G>T)?

AlphaMissense predicts likely pathogenic (score 0.9495) — an in-silico prediction, not a clinical call.

MYO7A p.Arg606Leu

c.1817G>T · rs782311929 · VCV2134433

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9495 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000347%, nfe)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9495	likely pathogenic
REVEL	0.912	moderately pathogenic-leaning
SaProt	LLR -12.85	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 8.6	GERP -0.43, 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 0.000347% European (non-Finnish) · 4/1,151,918 alleles

Filtering AF 8.1e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 5.5e-05%

Overall 0.000257% 4/1,558,530 alleles · very rare exomes 3/1,406,332 · genomes 1/152,198 · joint denominator

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.Arg606Leu
Coding: c.1817G>T
MANE Select: NM_000260
dbSNP: rs782311929
Type: single nucleotide variant
Location: chr11:77172767 (GRCh38)
Gene constraint: LOEUF 0.995 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.73 · 1 PDB
Residue 606: the myosin motor domain

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

Similar variants

MYO7A p.Arg606His Uncertain significance ★★★ ⚠ same residue
MYO7A p.Arg606Cys Uncertain significance ★★ ⚠ same residue
MYO7A p.Arg606Pro Uncertain significance ★ ⚠ same residue
MYO7A p.Arg606= Likely benign ★ 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

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-arg606leu (accessed [today's date]).

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