Is MYO7A p.Lys1727Gln (c.5179A>C) pathogenic?

MYO7A p.Lys1727Gln (c.5179A>C) is classified Uncertain significance in MYO7A (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-10-13). AlphaMissense: likely pathogenic (0.7066); Very rare (popmax 0.00196%, amr); Associated with Usher syndrome type 1B.

What condition is associated with MYO7A p.Lys1727Gln (c.5179A>C)?

MYO7A p.Lys1727Gln (c.5179A>C) is associated with Usher syndrome type 1B (ClinVar).

How common is MYO7A p.Lys1727Gln (c.5179A>C) in the general population?

MYO7A p.Lys1727Gln (c.5179A>C) is very rare (popmax 0.00196%, amr) (gnomAD).

What do computational predictors say about MYO7A p.Lys1727Gln (c.5179A>C)?

AlphaMissense predicts likely pathogenic (score 0.7066) — an in-silico prediction, not a clinical call.

MYO7A p.Lys1727Gln

c.5179A>C · rs1187644045 · VCV1035553

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely pathogenic

0.7066 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00196%, amr)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Usher syndrome type 1B

Computational evidence

Protein change
AlphaMissense	0.7066	likely pathogenic
REVEL	0.437	indeterminate
SaProt	LLR -6.80	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 11	GERP 1.8, phastCons 1
Regional constraint	o/e 0.95	unconstrained · MANE · 84 kb · p 0.0065 · regional, not allelic
Overall
CADD	26.2	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 0.00196% Admixed American · 1/50,994 alleles

Overall 6.46e-05% 1/1,548,000 alleles · very rare exomes 1/1,395,686 · genomes 0/152,314 · 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.Lys1727Gln
Coding: c.5179A>C
MANE Select: NM_000260
dbSNP: rs1187644045
Type: single nucleotide variant
Location: chr11:77203070 (GRCh38)
Gene constraint: LOEUF 0.995 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.73 · 1 PDB
Residue 1727: a turn

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

Disease context

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

Similar variants

MYO7A p.Lys1727Ter Likely pathogenic ★ 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-lys1727gln (accessed [today's date]).

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