Is MYO7A p.Lys502Asn (c.1506G>T) pathogenic?

MYO7A p.Lys502Asn (c.1506G>T) is classified Uncertain significance in MYO7A (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-09-26). AlphaMissense: likely pathogenic (0.9681); Very rare (popmax 0.00979%, amr); Associated with Inborn genetic diseases.

What condition is associated with MYO7A p.Lys502Asn (c.1506G>T)?

MYO7A p.Lys502Asn (c.1506G>T) is associated with Inborn genetic diseases (ClinVar).

How common is MYO7A p.Lys502Asn (c.1506G>T) in the general population?

MYO7A p.Lys502Asn (c.1506G>T) is very rare (popmax 0.00979%, amr) (gnomAD).

What do computational predictors say about MYO7A p.Lys502Asn (c.1506G>T)?

AlphaMissense predicts likely pathogenic (score 0.9681) — an in-silico prediction, not a clinical call.

MYO7A p.Lys502Asn

c.1506G>T · rs181126043 · VCV1351867

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.9681 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00979%, amr)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.9681	likely pathogenic
REVEL	0.684	pathogenic-leaning
SaProt	LLR -11.30	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3	GERP -0.42, phastCons 1
Regional constraint	o/e 0.95	unconstrained · MANE · 84 kb · p 0.0065 · regional, not allelic
Overall
CADD	22.8	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00979% Admixed American · 5/51,074 alleles

Filtering AF 0.00382% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00247%

Overall 0.000322% 5/1,553,198 alleles · very rare exomes 2/1,400,878 · genomes 3/152,320 · 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.Lys502Asn
Coding: c.1506G>T
MANE Select: NM_000260
dbSNP: rs181126043
Type: single nucleotide variant
Location: chr11:77162282 (GRCh38)
Gene constraint: LOEUF 0.995 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.73 · 1 PDB
Residue 502: the myosin motor domain

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

MYO7A p.Lys502= Likely benign ★★ same residue
MYO7A p.Ser1471Pro Pathogenic/Likely pathogenic ★★ same condition
MYO7A p.Ala1005Thr Uncertain significance ★★ ⚠ same condition
MYO7A p.Ala1203Ser Uncertain significance ★★ ⚠ same condition
MYO7A p.Ala1335Asp Uncertain significance ★★ ⚠ same condition
MYO7A p.Ala1551Val Uncertain significance ★★ ⚠ same condition
MYO7A p.Ala1563Val Uncertain significance ★★ ⚠ same condition
MYO7A p.Ala162Thr Uncertain significance ★★ ⚠ 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-lys502asn (accessed [today's date]).

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