Is MYO7A p.Thr1496= (c.4488G>A) pathogenic?

MYO7A p.Thr1496= (c.4488G>A) is classified Conflicting classifications of pathogenicity in MYO7A (ClinVar, Conflicting submitters, 4 submitters; last evaluated 2026-01-19). Ultra-rare (popmax 0.02%, amr); Associated with autosomal recessive nonsyndromic hearing loss 2.

What condition is associated with MYO7A p.Thr1496= (c.4488G>A)?

MYO7A p.Thr1496= (c.4488G>A) is associated with autosomal recessive nonsyndromic hearing loss 2, Usher syndrome type 1, autosomal dominant nonsyndromic hearing loss 11 (ClinVar).

How common is MYO7A p.Thr1496= (c.4488G>A) in the general population?

MYO7A p.Thr1496= (c.4488G>A) is ultra-rare (popmax 0.02%, amr) (gnomAD).

MYO7A p.Thr1496=

c.4488G>A · rs376743356 · VCV164705

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.02%, amr)

Conditions

autosomal recessive nonsyndromic hearing loss 2

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 -9.2	GERP -3.5
Overall
CADD	1.918	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.02% Admixed American · 12/60,026 alleles

Filtering AF 0.0115% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00898%

Overall 0.00483% 78/1,613,954 alleles · ultra-rare exomes 61/1,461,604 · genomes 17/152,350 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.02%	5,002
Remaining individualsnot grpmax-eligible	0.0064%	15,622
African / African-American	0.00533%	18,765
European (non-Finnish)	0.00483%	20,700
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,606

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.Thr1496=
Coding: c.4488G>A
MANE Select: NM_000260
dbSNP: rs376743356
Type: single nucleotide variant
Location: chr11:77198541 (GRCh38)
Gene constraint: LOEUF 0.995 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.73 · 1 PDB
Residue 1496: the ferm 1 domain

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

Disease context

autosomal recessive nonsyndromic hearing loss 2 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

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

Similar variants

MYO7A p.Thr1496Met Uncertain significance ★★ ⚠ same residue
MYO7A p.Thr1496Lys Conflicting classifications of pathogenicity ★ ⚠ 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

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-thr1496 (accessed [today's date]).

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