Is MYO7A p.Asp75Glu (c.225C>A) pathogenic?

MYO7A p.Asp75Glu (c.225C>A) is classified Uncertain significance in MYO7A (ClinVar, Multiple submitters, 5 submitters; last evaluated 2025-07-10). AlphaMissense: likely pathogenic (0.9462); Very rare (popmax 0.00495%, nfe); Associated with autosomal dominant nonsyndromic hearing loss 11.

What condition is associated with MYO7A p.Asp75Glu (c.225C>A)?

MYO7A p.Asp75Glu (c.225C>A) is associated with autosomal dominant nonsyndromic hearing loss 11, Usher syndrome type 1, autosomal recessive nonsyndromic hearing loss 2 (ClinVar).

How common is MYO7A p.Asp75Glu (c.225C>A) in the general population?

MYO7A p.Asp75Glu (c.225C>A) is very rare (popmax 0.00495%, nfe) (gnomAD).

What do computational predictors say about MYO7A p.Asp75Glu (c.225C>A)?

AlphaMissense predicts likely pathogenic (score 0.9462) — an in-silico prediction, not a clinical call.

MYO7A p.Asp75Glu

c.225C>A · rs782757893 · VCV306156

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

AlphaMissense

likely pathogenic

0.9462 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00495%, nfe)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

autosomal dominant nonsyndromic hearing loss 11

Computational evidence

Protein change
AlphaMissense	0.9462	likely pathogenic
REVEL	0.562	indeterminate
SaProt	LLR -9.32	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.23	GERP -0.39, phastCons 0.98
Regional constraint	o/e 0.95	unconstrained · MANE · 84 kb · p 0.0065 · regional, not allelic
Overall
CADD	21.8	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00495% European (non-Finnish) · 58/1,171,222 alleles

Filtering AF 0.00389% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00355%

Overall 0.00389% 62/1,593,686 alleles · very rare exomes 57/1,441,524 · genomes 5/152,162 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00495%	20,193
Admixed American	0.00349%	28,634
Remaining individualsnot grpmax-eligible	0.00324%	30,878

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.Asp75Glu
Coding: c.225C>A
MANE Select: NM_000260
dbSNP: rs782757893
Type: single nucleotide variant
Location: chr11:77147890 (GRCh38)
Gene constraint: LOEUF 0.995 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.73 · 1 PDB
Residue 75: the myosin motor domain

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

Disease context

autosomal dominant nonsyndromic hearing loss 11 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

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

Similar variants

MYO7A p.Asp75= Uncertain significance same residue
MYO7A p.Asp75fs Pathogenic ★ same residue
MYO7A p.Asp75His 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

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-asp75glu (accessed [today's date]).

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