Is MYO7A p.Thr1234= (c.3702C>G) pathogenic?

MYO7A p.Thr1234= (c.3702C>G) is classified Conflicting classifications of pathogenicity in MYO7A (ClinVar, Conflicting submitters, 6 submitters; last evaluated 2026-01-20). Rare (popmax 0.244%, eas); Associated with Inborn genetic diseases.

What condition is associated with MYO7A p.Thr1234= (c.3702C>G)?

MYO7A p.Thr1234= (c.3702C>G) is associated with Inborn genetic diseases, Usher syndrome type 1, autosomal recessive nonsyndromic hearing loss 2 (ClinVar).

How common is MYO7A p.Thr1234= (c.3702C>G) in the general population?

MYO7A p.Thr1234= (c.3702C>G) is rare (popmax 0.244%, eas) (gnomAD).

MYO7A p.Thr1234=

c.3702C>G · rs77299211 · VCV227682

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 6 submitters

gnomAD v4.1

Rare

rare (popmax 0.244%, eas)

Conditions

Inborn genetic diseases

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 -0.22	GERP -1.9, phastCons 0.22
Overall
CADD	2.97	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.244% East Asian · 105/43,058 alleles

Filtering AF 0.206% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.192%

Overall 0.00766% 121/1,579,620 alleles · rare exomes 113/1,427,268 · genomes 8/152,352 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.244%	410
South Asian	0.0139%	7,173
Remaining individualsnot grpmax-eligible	0.0049%	20,405
European (non-Finnish)	8.6e-05%	1,163,431

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.Thr1234=
Coding: c.3702C>G
MANE Select: NM_000260
dbSNP: rs77299211
Type: single nucleotide variant
Location: chr11:77190091 (GRCh38)
Gene constraint: LOEUF 0.995 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.73 · 1 PDB
Residue 1234: the myth4 1 domain

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: Usher syndrome type 1 autosomal recessive nonsyndromic hearing loss 2 autosomal dominant nonsyndromic hearing loss 11

Similar variants

MYO7A p.Thr1234Ser 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-thr1234 (accessed [today's date]).

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