Is MYO7A p.Gly2137Arg (c.6409G>A) pathogenic?

MYO7A p.Gly2137Arg (c.6409G>A) is classified Likely pathogenic in MYO7A (ClinVar, Multiple submitters, 3 submitters; last evaluated 2021-10-20). AlphaMissense: likely pathogenic (0.9981); Very rare (popmax 8.56e-05%, nfe); Associated with inherited retinal dystrophy.

What condition is associated with MYO7A p.Gly2137Arg (c.6409G>A)?

MYO7A p.Gly2137Arg (c.6409G>A) is associated with inherited retinal dystrophy, autosomal dominant nonsyndromic hearing loss 11 (ClinVar).

How common is MYO7A p.Gly2137Arg (c.6409G>A) in the general population?

MYO7A p.Gly2137Arg (c.6409G>A) is very rare (popmax 8.56e-05%, nfe) (gnomAD).

What do computational predictors say about MYO7A p.Gly2137Arg (c.6409G>A)?

AlphaMissense predicts likely pathogenic (score 0.9981) — an in-silico prediction, not a clinical call.

MYO7A p.Gly2137Arg

c.6409G>A · rs1223784415 · VCV931720

Likely pathogenic Multiple submitters

Classification

Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely pathogenic

0.9981 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.56e-05%, nfe)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

inherited retinal dystrophy

Computational evidence

Protein change
AlphaMissense	0.9981	likely pathogenic ✓ concordant with ClinVar · top 3% in MYO7A
REVEL	0.862	moderately pathogenic-leaning
SaProt	LLR -17.76	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 12	GERP 1.8, phastCons 1
Regional constraint	o/e 0.95	unconstrained · MANE · 84 kb · p 0.0065 · regional, not allelic
Overall
CADD	30.0	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 8.56e-05% European (non-Finnish) · 1/1,167,774 alleles

Overall 0.000126% 2/1,590,436 alleles · very rare exomes 2/1,438,240 · genomes 0/152,196 · joint denominator

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.00162%	61,748
European (non-Finnish)grpmax	8.56e-05%	1,167,774

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Gly2137Arg
Coding: c.6409G>A
MANE Select: NM_000260
dbSNP: rs1223784415
Type: single nucleotide variant
Location: chr11:77213006 (GRCh38)
Gene constraint: LOEUF 0.995 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.73 · 1 PDB
Residue 2137: the ferm 2 domain; a β-strand; a UniProt-annotated variant site (in ush1b)

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

Disease context

inherited retinal dystrophy — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: autosomal dominant nonsyndromic hearing loss 11

Similar variants

MYO7A p.Gly2137= Uncertain significance 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
MYO7A p.Glu968Asp 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-gly2137arg (accessed [today's date]).

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