Is MYO7A p.Arg858= (c.2574C>T) pathogenic?

MYO7A p.Arg858= (c.2574C>T) is classified Likely benign in MYO7A (ClinVar, Single submitter, 1 submitter; last evaluated 2021-09-19). Very rare (popmax 8.78e-05%, nfe).

How common is MYO7A p.Arg858= (c.2574C>T) in the general population?

MYO7A p.Arg858= (c.2574C>T) is very rare (popmax 8.78e-05%, nfe) (gnomAD).

MYO7A p.Arg858=

c.2574C>T · rs1555083013 · VCV1605836

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 8.78e-05%, nfe)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.77	GERP -1.8, phastCons 1
Overall
CADD	10.37	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.78e-05% European (non-Finnish) · 1/1,138,504 alleles

Overall 6.55e-05% 1/1,527,076 alleles · very rare exomes 1/1,374,682 · genomes 0/152,394 · 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.Arg858=
Coding: c.2574C>T
MANE Select: NM_000260
dbSNP: rs1555083013
Type: single nucleotide variant
Location: chr11:77179941 (GRCh38)
Gene constraint: LOEUF 0.995 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.73 · 1 PDB
Residue 858: the 'sah' region

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

Similar variants

MYO7A p.Arg858Cys Uncertain significance ★★ same residue
MYO7A p.Arg858His Conflicting classifications of pathogenicity ★ ⚠ same residue
MYO7A p.Arg858Leu 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

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-arg858 (accessed [today's date]).

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