Is MYO7A p.Lys1384Asn (c.4152G>C) pathogenic?

MYO7A p.Lys1384Asn (c.4152G>C) is classified Likely pathogenic in MYO7A (ClinVar, Single submitter, 1 submitter; last evaluated 2022-07-17). AlphaMissense: likely pathogenic (0.7744); Very rare (popmax 0.00017%, nfe); Associated with MYO7A-related disorder.

What condition is associated with MYO7A p.Lys1384Asn (c.4152G>C)?

MYO7A p.Lys1384Asn (c.4152G>C) is associated with MYO7A-related disorder (ClinVar).

How common is MYO7A p.Lys1384Asn (c.4152G>C) in the general population?

MYO7A p.Lys1384Asn (c.4152G>C) is very rare (popmax 0.00017%, nfe) (gnomAD).

What do computational predictors say about MYO7A p.Lys1384Asn (c.4152G>C)?

AlphaMissense predicts likely pathogenic (score 0.7744) — an in-silico prediction, not a clinical call.

MYO7A p.Lys1384Asn

c.4152G>C · VCV4913259

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7744 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00017%, nfe)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

MYO7A-related disorder

Computational evidence

Protein change
AlphaMissense	0.7744	likely pathogenic ✓ concordant with ClinVar
REVEL	0.551	indeterminate
SaProt	LLR -4.76	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL is indeterminate.
Splicing
SpliceAI	Δ0.61	donor loss · deltas
Pangolin	Δ0.57	loss · gain 0.46 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 9.9	GERP 1.4, phastCons 1
Regional constraint	o/e 0.95	unconstrained · MANE · 84 kb · p 0.0065 · regional, not allelic
Overall
CADD	35.0	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 0.00017% European (non-Finnish) · 2/1,179,516 alleles

Filtering AF 2.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000124% 2/1,613,604 alleles · very rare exomes 2/1,461,232 · genomes 0/152,372 · 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.Lys1384Asn
Coding: c.4152G>C
MANE Select: NM_000260
Type: single nucleotide variant
Location: chr11:77192278 (GRCh38)
Gene constraint: LOEUF 0.995 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.73 · 1 PDB
Residue 1384: the ferm 1 domain

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

Disease context

MYO7A-related disorder

Similar variants

MYO7A c.133-2A>G Pathogenic ★★ same condition
MYO7A c.1344-2A>G Pathogenic ★★ same condition
MYO7A c.1690+1G>A Pathogenic/Likely pathogenic ★★ same condition
MYO7A c.18+1G>A Pathogenic/Likely pathogenic ★★ same condition
MYO7A c.19-1G>A Likely pathogenic ★★ same condition
MYO7A c.2187+1G>A Pathogenic/Likely pathogenic ★★ same condition
MYO7A c.2283-1G>A Pathogenic/Likely pathogenic ★★ same condition
MYO7A c.2694+1G>A 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-lys1384asn (accessed [today's date]).

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