Is MYO7A p.Phe678= (c.2034C>T) pathogenic?

MYO7A p.Phe678= (c.2034C>T) is classified Likely benign in MYO7A (ClinVar, Multiple submitters, 4 submitters; last evaluated 2025-12-14). Ultra-rare (popmax 0.0329%, mid); Associated with Usher syndrome type 1B.

What condition is associated with MYO7A p.Phe678= (c.2034C>T)?

MYO7A p.Phe678= (c.2034C>T) is associated with Usher syndrome type 1B (ClinVar).

How common is MYO7A p.Phe678= (c.2034C>T) in the general population?

MYO7A p.Phe678= (c.2034C>T) is ultra-rare (popmax 0.0329%, mid) (gnomAD).

MYO7A p.Phe678=

c.2034C>T · rs782519043 · VCV991217

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0329%, 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	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -14	GERP -3.5
Overall
CADD	3.938	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0329% Middle Eastern · 2/6,084 alleles

Filtering AF 0.0058% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00241%

Overall 0.00254% 41/1,613,610 alleles · ultra-rare exomes 40/1,461,408 · genomes 1/152,202 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0329%	3,042
European (non-Finnish)	0.00288%	34,703
East Asian	0.00223%	44,882
Admixed American	0.00167%	59,998
Remaining individualsnot grpmax-eligible	0.0016%	62,462
African / African-American	0.00133%	74,940
South Asian	0.0011%	91,088

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.Phe678=
Coding: c.2034C>T
MANE Select: NM_000260
dbSNP: rs782519043
Type: single nucleotide variant
Location: chr11:77174854 (GRCh38)
Gene constraint: LOEUF 0.995 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.73 · 1 PDB
Residue 678: 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.Phe678Leu 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-phe678 (accessed [today's date]).

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