Is MYO7A p.Asp908Glu (c.2724C>G) pathogenic?

MYO7A p.Asp908Glu (c.2724C>G) is classified Likely benign in MYO7A (ClinVar, Single submitter, 2 submitters; last evaluated 2026-01-05). AlphaMissense: likely benign (0.197); Rare (popmax 0.12%, eas); Associated with Usher syndrome type 1.

What condition is associated with MYO7A p.Asp908Glu (c.2724C>G)?

MYO7A p.Asp908Glu (c.2724C>G) is associated with Usher syndrome type 1, autosomal recessive nonsyndromic hearing loss 2 (ClinVar).

How common is MYO7A p.Asp908Glu (c.2724C>G) in the general population?

MYO7A p.Asp908Glu (c.2724C>G) is rare (popmax 0.12%, eas) (gnomAD).

How is Usher syndrome inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

What do computational predictors say about MYO7A p.Asp908Glu (c.2724C>G)?

AlphaMissense predicts likely benign (score 0.197) — an in-silico prediction, not a clinical call.

MYO7A p.Asp908Glu

c.2724C>G · rs199979876 · VCV552676

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.197 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.12%, eas)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Usher syndrome type 1

Computational evidence

Protein change
AlphaMissense	0.197	likely benign
REVEL	0.304	indeterminate
SaProt	LLR -3.08	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -12	GERP -3.2
Regional constraint	o/e 0.95	unconstrained · MANE · 84 kb · p 0.0065 · regional, not allelic
Overall
CADD	0.015	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 0.12% East Asian · 52/43,266 alleles

Filtering AF 0.0941% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0848%

Overall 0.00335% 53/1,581,218 alleles · rare exomes 52/1,428,866 · genomes 1/152,352 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.12%	832
Admixed American	0.00183%	54,792

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.Asp908Glu
Coding: c.2724C>G
MANE Select: NM_000260
dbSNP: rs199979876
Type: single nucleotide variant
Location: chr11:77181409 (GRCh38)
Gene constraint: LOEUF 0.995 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.73 · 1 PDB
Residue 908: the 'sah' region

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

Disease context

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

Also linked: autosomal recessive nonsyndromic hearing loss 2

For Usher syndrome (Orphanet):

Inheritance: Autosomal recessive
Onset: Childhood, Infancy, Neonatal
Prevalence: 1-9 / 100 000 (Worldwide)

Similar variants

MYO7A p.Asp908= 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
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-asp908glu (accessed [today's date]).

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