Is MYO7A p.His1318= (c.3954C>T) pathogenic?

MYO7A p.His1318= (c.3954C>T) is classified Likely benign in MYO7A (ClinVar, Multiple submitters, 6 submitters; last evaluated 2025-08-26). Ultra-rare (popmax 0.0187%, afr); Associated with Usher syndrome type 1B.

What condition is associated with MYO7A p.His1318= (c.3954C>T)?

MYO7A p.His1318= (c.3954C>T) is associated with Usher syndrome type 1B (ClinVar).

How common is MYO7A p.His1318= (c.3954C>T) in the general population?

MYO7A p.His1318= (c.3954C>T) is ultra-rare (popmax 0.0187%, afr) (gnomAD).

MYO7A p.His1318=

c.3954C>T · rs749218462 · VCV799469

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0187%, afr)

Conditions

Usher syndrome type 1B

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -9.3	GERP -2.8
Overall
CADD	1.749	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0187% African / African-American · 14/74,958 alleles

Filtering AF 0.0112% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00904%

Overall 0.00378% 61/1,613,632 alleles · ultra-rare exomes 50/1,461,372 · genomes 11/152,260 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0187%	5,354
Admixed American	0.0183%	5,455
South Asian	0.00549%	18,214
Remaining individualsnot grpmax-eligible	0.0048%	20,818
East Asian	0.00446%	22,445
European (non-Finnish)	0.0022%	45,381

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.His1318=
Coding: c.3954C>T
MANE Select: NM_000260
dbSNP: rs749218462
Type: single nucleotide variant
Location: chr11:77192080 (GRCh38)
Gene constraint: LOEUF 0.995 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.73 · 1 PDB
Residue 1318: the ferm 1 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.His1318fs Likely pathogenic ★ 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-his1318 (accessed [today's date]).

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