Is MYO7A p.Lys1348fs (c.4043_4044del) pathogenic?

MYO7A p.Lys1348fs (c.40434044del) is classified Pathogenic in MYO7A (ClinVar, Single submitter, 1 submitter; last evaluated 2022-02-03). Very rare (popmax 0.00133%, afr).

How common is MYO7A p.Lys1348fs (c.4043_4044del) in the general population?

MYO7A p.Lys1348fs (c.4043_4044del) is very rare (popmax 0.00133%, afr) (gnomAD).

MYO7A p.Lys1348fs

c.4043_4044del · rs2497411466 · VCV2089419

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00133%, afr)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 31 of 49
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -1.4	GERP -3.1

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00133% African / African-American · 1/75,070 alleles

Overall 6.2e-05% 1/1,614,024 alleles · very rare exomes 1/1,461,654 · genomes 0/152,370 · 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.Lys1348fs
Coding: c.4043_4044del
MANE Select: NM_000260
dbSNP: rs2497411466
Type: Deletion
Location: chr11:77192168 (GRCh38)
Gene constraint: LOEUF 0.995 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.73 · 1 PDB
Residue 1348: the ferm 1 domain; a UniProt-annotated variant site (in ush1b)

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

Similar variants

MYO7A c.3503+12_3503+33del Benign ★★★ same type
MYO7A c.2187+2_2187+8del Pathogenic/Likely pathogenic ★★ same type
MYO7A c.2283-2_2293del Pathogenic/Likely pathogenic ★★ same type
MYO7A c.5471_5480+5del Pathogenic/Likely pathogenic ★★ same type
MYO7A p.Ala1277fs Pathogenic/Likely pathogenic ★★ same type
MYO7A p.Ala2009fs Pathogenic ★★ same type
MYO7A p.Ala202fs Pathogenic/Likely pathogenic ★★ same type
MYO7A p.Ala353_Thr354insTer Pathogenic/Likely pathogenic ★★ same type

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-lys1348fs (accessed [today's date]).

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