Is MYO7A p.Lys1952= (c.5856G>A) pathogenic?

MYO7A p.Lys1952= (c.5856G>A) is classified Pathogenic/Likely pathogenic in MYO7A (ClinVar, Multiple submitters, 5 submitters; last evaluated 2025-10-28). Very rare (popmax 0.00171%, amr); Associated with MYO7A-related disorder.

What condition is associated with MYO7A p.Lys1952= (c.5856G>A)?

MYO7A p.Lys1952= (c.5856G>A) is associated with MYO7A-related disorder, Usher syndrome type 1, autosomal recessive nonsyndromic hearing loss 2 (ClinVar).

How common is MYO7A p.Lys1952= (c.5856G>A) in the general population?

MYO7A p.Lys1952= (c.5856G>A) is very rare (popmax 0.00171%, amr) (gnomAD).

MYO7A p.Lys1952=

c.5856G>A · rs1453053718 · VCV556557

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00171%, amr)

Conditions

MYO7A-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Splicing
SpliceAI	Δ0.79	donor gain · deltas
Pangolin	Δ0.57	loss · gain 0.49 · SpliceAI calls gain · independent
Constraint at this position
Conservation	phyloP 9.9	GERP 1.7, phastCons 1
Overall
CADD	24.7	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00171% Admixed American · 1/58,590 alleles

Overall 0.000188% 3/1,599,736 alleles · very rare exomes 2/1,447,540 · genomes 1/152,196 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00171%	58,590
African / African-American	0.00134%	74,620
European (non-Finnish)	8.54e-05%	1,171,637

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.Lys1952=
Coding: c.5856G>A
MANE Select: NM_000260
dbSNP: rs1453053718
Type: single nucleotide variant
Location: chr11:77207402 (GRCh38)
Gene constraint: LOEUF 0.995 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.73 · 1 PDB
Residue 1952: the ferm 2 domain

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 Usher syndrome type 1B

Similar variants

MYO7A p.Lys1952Ter 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-lys1952 (accessed [today's date]).

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