Is MYO7A p.Gly1842= (c.5526C>T) pathogenic?

MYO7A p.Gly1842= (c.5526C>T) is classified Likely benign in MYO7A (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-01-28). Ultra-rare (popmax 0.0242%, afr).

How common is MYO7A p.Gly1842= (c.5526C>T) in the general population?

MYO7A p.Gly1842= (c.5526C>T) is ultra-rare (popmax 0.0242%, afr) (gnomAD).

MYO7A p.Gly1842=

c.5526C>T · rs776406549 · VCV1117418

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0242%, afr)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Splicing
SpliceAI	Δ0.38	acceptor gain · deltas
Pangolin	Δ0.28	gain · loss 0.13 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 0.12	GERP -2.2, phastCons 0.91
Overall
CADD	16.77	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0242% African / African-American · 18/74,476 alleles

Filtering AF 0.0156% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0129%

Overall 0.00275% 44/1,598,830 alleles · ultra-rare exomes 31/1,446,668 · genomes 13/152,162 · joint denominator

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	0.0411%	2,434
African / African-Americangrpmax	0.0242%	4,138
Remaining individualsnot grpmax-eligible	0.00646%	15,471
European (non-Finnish)	0.000852%	117,357

Ashkenazi Jewish 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.Gly1842=
Coding: c.5526C>T
MANE Select: NM_000260
dbSNP: rs776406549
Type: single nucleotide variant
Location: chr11:77205507 (GRCh38)
Gene constraint: LOEUF 0.995 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.73 · 1 PDB
Residue 1842: the myth4 2 domain

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

Similar variants

MYO7A p.Gly1842fs Pathogenic ★★ 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-gly1842 (accessed [today's date]).

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