Is MYO7A p.Asp2010Asn (c.6028G>A) pathogenic?

MYO7A p.Asp2010Asn (c.6028G>A) is classified Pathogenic/Likely pathogenic in MYO7A (ClinVar, Multiple submitters, 8 submitters; last evaluated 2026-01-07). AlphaMissense: likely pathogenic (0.8394); Ultra-rare (popmax 0.0136%, afr); Associated with MYO7A-related disorder.

What condition is associated with MYO7A p.Asp2010Asn (c.6028G>A)?

MYO7A p.Asp2010Asn (c.6028G>A) is associated with MYO7A-related disorder, Usher syndrome type 1, autosomal recessive nonsyndromic hearing loss 2 (ClinVar).

How common is MYO7A p.Asp2010Asn (c.6028G>A) in the general population?

MYO7A p.Asp2010Asn (c.6028G>A) is ultra-rare (popmax 0.0136%, afr) (gnomAD).

What do computational predictors say about MYO7A p.Asp2010Asn (c.6028G>A)?

AlphaMissense predicts likely pathogenic (score 0.8394) — an in-silico prediction, not a clinical call.

MYO7A p.Asp2010Asn

c.6028G>A · rs755934966 · VCV551533

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 8 submitters

AlphaMissense

likely pathogenic

0.8394 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0136%, afr)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

MYO7A-related disorder

Computational evidence

Protein change
AlphaMissense	0.8394	likely pathogenic ✓ concordant with ClinVar
REVEL	0.66	pathogenic-leaning
SaProt	LLR -14.03	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 1.8, phastCons 1
Regional constraint	o/e 0.95	unconstrained · MANE · 84 kb · p 0.0065 · regional, not allelic
Overall
CADD	31.0	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 0.0136% African / African-American · 10/73,790 alleles

Filtering AF 0.00733% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00557%

Overall 0.00102% 16/1,570,436 alleles · ultra-rare exomes 6/1,418,232 · genomes 10/152,204 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0136%	7,379
Admixed American	0.00371%	26,979
Finnishnot grpmax-eligible	0.00327%	30,538
South Asian	0.00235%	42,574

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.Asp2010Asn
Coding: c.6028G>A
MANE Select: NM_000260
dbSNP: rs755934966
Type: single nucleotide variant
Location: chr11:77208780 (GRCh38)
Gene constraint: LOEUF 0.995 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.73 · 1 PDB
Residue 2010: the ferm 2 domain; an α-helix

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

Disease context

MYO7A-related disorder

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

Similar variants

MYO7A p.Asp2010Gly Likely pathogenic ★ same residue
MYO7A p.Asp2010Tyr Likely pathogenic ★ same residue
MYO7A p.Asp2010= Likely benign ★ 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-asp2010asn (accessed [today's date]).

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