Is MYO7A p.Arg378= (c.1134C>T) pathogenic?

MYO7A p.Arg378= (c.1134C>T) is classified Likely benign in MYO7A (ClinVar, Single submitter, 1 submitter; last evaluated 2024-11-03). Very rare (popmax 0.00405%, afr).

How common is MYO7A p.Arg378= (c.1134C>T) in the general population?

MYO7A p.Arg378= (c.1134C>T) is very rare (popmax 0.00405%, afr) (gnomAD).

MYO7A p.Arg378=

c.1134C>T · rs1213402972 · VCV1082311

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00405%, afr)

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 -20	GERP -3.2
Overall
CADD	0.532	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00405% African / African-American · 3/74,086 alleles

Filtering AF 0.00124% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00106%

Overall 0.0019% 30/1,581,462 alleles · very rare exomes 26/1,429,288 · genomes 4/152,174 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00405%	24,695
South Asian	0.00233%	42,952
European (non-Finnish)	0.00189%	52,930
Admixed American	0.00179%	55,724
Finnishnot grpmax-eligible	0.00163%	61,274
Remaining individualsnot grpmax-eligible	0.00163%	61,284

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.Arg378=
Coding: c.1134C>T
MANE Select: NM_000260
dbSNP: rs1213402972
Type: single nucleotide variant
Location: chr11:77160216 (GRCh38)
Gene constraint: LOEUF 0.995 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.73 · 1 PDB
Residue 378: the myosin motor domain

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

Similar variants

MYO7A p.Arg378His Uncertain significance ★★ ⚠ same residue
MYO7A p.Arg378Cys Conflicting classifications of pathogenicity ★ ⚠ same residue
MYO7A p.Arg378Leu Uncertain significance ★ ⚠ same residue
MYO7A p.Arg378Pro 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

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-arg378 (accessed [today's date]).

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