Is MYO7A p.Ser115= (c.345G>A) pathogenic?

MYO7A p.Ser115= (c.345G>A) is classified Likely benign in MYO7A (ClinVar, Single submitter, 2 submitters; last evaluated 2025-12-23). Ultra-rare (popmax 0.0164%, mid); Associated with Usher syndrome type 1B.

What condition is associated with MYO7A p.Ser115= (c.345G>A)?

MYO7A p.Ser115= (c.345G>A) is associated with Usher syndrome type 1B (ClinVar).

How common is MYO7A p.Ser115= (c.345G>A) in the general population?

MYO7A p.Ser115= (c.345G>A) is ultra-rare (popmax 0.0164%, mid) (gnomAD).

MYO7A p.Ser115=

c.345G>A · rs781980240 · VCV1130844

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0164%, mid)

Conditions

Usher syndrome type 1B

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>C here scores Δ0.57 · evaluated, not missing
Constraint at this position
Conservation	phyloP -4.1	GERP -3.8
Overall
CADD	10.68	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0164% Middle Eastern · 1/6,084 alleles

Filtering AF 0.00324% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00207%

Overall 0.000992% 16/1,612,652 alleles · ultra-rare exomes 15/1,460,474 · genomes 1/152,178 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0164%	6,084
Admixed American	0.00836%	11,964
African / African-American	0.00401%	24,964
European (non-Finnish)	0.000594%	168,489

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.Ser115=
Coding: c.345G>A
MANE Select: NM_000260
dbSNP: rs781980240
Type: single nucleotide variant
Location: chr11:77155966 (GRCh38)
Gene constraint: LOEUF 0.995 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.73 · 1 PDB
Residue 115: the myosin motor domain

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

Disease context

Usher syndrome type 1B — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

MYO7A p.Ser115Leu Uncertain significance ★ ⚠ 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-ser115 (accessed [today's date]).

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