Is MYO7A p.Asn1848Ile (c.5543A>T) pathogenic?

MYO7A p.Asn1848Ile (c.5543A>T) is classified Uncertain significance in MYO7A (ClinVar, Single submitter, 1 submitter; last evaluated 2025-03-07). AlphaMissense: ambiguous (0.5578); Absent from gnomAD v4.1; Associated with autosomal dominant nonsyndromic hearing loss 11.

What condition is associated with MYO7A p.Asn1848Ile (c.5543A>T)?

MYO7A p.Asn1848Ile (c.5543A>T) is associated with autosomal dominant nonsyndromic hearing loss 11 (ClinVar).

How common is MYO7A p.Asn1848Ile (c.5543A>T) in the general population?

MYO7A p.Asn1848Ile (c.5543A>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about MYO7A p.Asn1848Ile (c.5543A>T)?

AlphaMissense predicts ambiguous (score 0.5578) — an in-silico prediction, not a clinical call.

MYO7A p.Asn1848Ile

c.5543A>T · rs764485686 · VCV4687904

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5578 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

autosomal dominant nonsyndromic hearing loss 11

Computational evidence

Protein change
AlphaMissense	0.5578	ambiguous
REVEL	0.641	indeterminate
SaProt	LLR -10.21	damaging
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 1.8	GERP 0.22, phastCons 0.4
Regional constraint	o/e 0.95	unconstrained · MANE · 84 kb · p 0.0065 · regional, not allelic
Overall
CADD	20.1	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: MYO7A
Protein: p.Asn1848Ile
Coding: c.5543A>T
MANE Select: NM_000260
dbSNP: rs764485686
Type: single nucleotide variant
Location: chr11:77205524 (GRCh38)
Gene constraint: LOEUF 0.995 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.73 · 1 PDB
Residue 1848: the myth4 2 domain; a turn

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

Similar variants

MYO7A p.Asn1848= Likely benign ★ same residue
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
MYO7A p.His133Asn 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-asn1848ile (accessed [today's date]).

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