Is MYO7A c.18+1G>A pathogenic?

MYO7A c.18+1G>A is classified Pathogenic/Likely pathogenic in MYO7A (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-10-11). Very rare (popmax 8.48e-05%, nfe); Associated with MYO7A-related disorder.

What condition is associated with MYO7A c.18+1G>A?

MYO7A c.18+1G>A is associated with MYO7A-related disorder (ClinVar).

How common is MYO7A c.18+1G>A in the general population?

MYO7A c.18+1G>A is very rare (popmax 8.48e-05%, nfe) (gnomAD).

MYO7A c.18+1G>A

rs2496360223 · VCV2711287

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

Consequence

canonical splice-site (±1/±2)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 8.48e-05%, nfe)

Conditions

MYO7A-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Consequence	canonical splice-site (±1/±2)	predicted loss-of-function
Splicing
Splice region	donor +1	canonical splice dinucleotide (donor +1) · inside the BP7-excluded zone
SpliceAI	Δ0.98	donor loss · deltas
Pangolin	Δ0.83	loss · gain 0.02 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 11	GERP 2.1, phastCons 1
Overall
CADD	32.0	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.48e-05% European (non-Finnish) · 1/1,179,700 alleles

Overall 6.2e-05% 1/1,613,314 alleles · very rare exomes 1/1,460,994 · genomes 0/152,320 · 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
Coding: c.18+1G>A
MANE Select: NM_000260
dbSNP: rs2496360223
Type: single nucleotide variant
Location: chr11:77130653 (GRCh38)
Gene constraint: LOEUF 0.995 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.73 · 1 PDB

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.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
MYO7A c.285+2T>A Pathogenic/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-c-18-plus-1g-a (accessed [today's date]).

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