Is MYO7A p.Thr842= (c.2526C>T) pathogenic?

MYO7A p.Thr842= (c.2526C>T) is classified Likely benign in MYO7A (ClinVar, Single submitter, 2 submitters; last evaluated 2026-01-20). Very rare (popmax 0.00589%, amr); Associated with Usher syndrome type 1B.

What condition is associated with MYO7A p.Thr842= (c.2526C>T)?

MYO7A p.Thr842= (c.2526C>T) is associated with Usher syndrome type 1B (ClinVar).

How common is MYO7A p.Thr842= (c.2526C>T) in the general population?

MYO7A p.Thr842= (c.2526C>T) is very rare (popmax 0.00589%, amr) (gnomAD).

MYO7A p.Thr842=

c.2526C>T · rs782594184 · VCV796379

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00589%, amr)

Conditions

Usher syndrome type 1B

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Splicing
SpliceAI	Δ0.23	donor gain · deltas
Constraint at this position
Conservation	phyloP -20	GERP -3.5
Overall
CADD	9.08	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00589% Admixed American · 3/50,962 alleles

Filtering AF 0.00156% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000833%

Overall 0.000649% 10/1,539,692 alleles · very rare exomes 7/1,387,434 · genomes 3/152,258 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00589%	16,987
African / African-American	0.00411%	24,343
South Asian	0.00357%	27,987
European (non-Finnish)	8.72e-05%	1,146,332

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.Thr842=
Coding: c.2526C>T
MANE Select: NM_000260
dbSNP: rs782594184
Type: single nucleotide variant
Location: chr11:77179893 (GRCh38)
Gene constraint: LOEUF 0.995 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.73 · 1 PDB
Residue 842: the iq 5 domain

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

Disease context

Usher syndrome type 1B — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

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
MYO7A p.Gly2187Asp 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-thr842 (accessed [today's date]).

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