What condition is associated with MYO7A p.Lys1741Glu (c.5221A>G)?

MYO7A p.Lys1741Glu (c.5221A>G) is associated with autosomal dominant nonsyndromic hearing loss 11 (ClinVar).

How common is MYO7A p.Lys1741Glu (c.5221A>G) in the general population?

MYO7A p.Lys1741Glu (c.5221A>G) is very rare (popmax 0.00244%, eas) (gnomAD).

What do computational predictors say about MYO7A p.Lys1741Glu (c.5221A>G)?

AlphaMissense predicts likely pathogenic (score 0.5969) — an in-silico prediction, not a clinical call.

MYO7A p.Lys1741Glu

Q: Is MYO7A p.Lys1741Glu (c.5221A>G) pathogenic?

MYO7A p.Lys1741Glu (c.5221A>G) is classified Uncertain significance in MYO7A (ClinVar, Single submitter, 1 submitter). AlphaMissense: likely pathogenic (0.5969); Very rare (popmax 0.00244%, eas); Associated with autosomal dominant nonsyndromic hearing loss 11.

c.5221A>G · rs1957185407 · VCV1339095

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.5969 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00244%, eas)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

autosomal dominant nonsyndromic hearing loss 11

Computational evidence

Protein change
AlphaMissense	0.5969	likely pathogenic
REVEL	0.463	indeterminate
SaProt	LLR -7.53	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 8.1	GERP -0.52, phastCons 1
Regional constraint	o/e 0.95	unconstrained · MANE · 84 kb · p 0.0065 · regional, not allelic
Overall
CADD	24.3	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 0.00244% East Asian · 1/40,962 alleles

Overall 6.45e-05% 1/1,549,480 alleles · very rare exomes 1/1,397,142 · genomes 0/152,338 · joint denominator

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.Lys1741Glu
Coding: c.5221A>G
MANE Select: NM_000260
dbSNP: rs1957185407
Type: single nucleotide variant
Location: chr11:77203112 (GRCh38)
Gene constraint: LOEUF 0.995 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.73 · 1 PDB

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.Lys1741Asn Uncertain significance ★ ⚠ 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-lys1741glu (accessed [today's date]).

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