Is MYO7A p.Phe1963del (c.5880CTT[2]) pathogenic?

MYO7A p.Phe1963del (c.5880CTT[2]) is classified Pathogenic/Likely pathogenic in MYO7A (ClinVar, Multiple submitters, 10 submitters; last evaluated 2025-02-18). Very rare (popmax 0.00668%, eas); Associated with MYO7A-related disorder.

What condition is associated with MYO7A p.Phe1963del (c.5880CTT[2])?

MYO7A p.Phe1963del (c.5880CTT[2]) is associated with MYO7A-related disorder, Usher syndrome type 1, autosomal recessive nonsyndromic hearing loss 2 (ClinVar).

How common is MYO7A p.Phe1963del (c.5880CTT[2]) in the general population?

MYO7A p.Phe1963del (c.5880CTT[2]) is very rare (popmax 0.00668%, eas) (gnomAD).

MYO7A p.Phe1963del

c.5880CTT[2] · rs111033232 · VCV43308

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 10 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00668%, eas)

Conditions

MYO7A-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 11	GERP 1.6, phastCons 1
Overall
CADD	17.99	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00668% East Asian · 3/44,878 alleles

Filtering AF 0.00177% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000891%

Overall 0.00248% 40/1,613,408 alleles · very rare exomes 35/1,461,262 · genomes 5/152,146 · joint denominator

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	0.0188%	5,332
East Asiangrpmax	0.00668%	14,959
African / African-American	0.004%	24,974
Remaining individualsnot grpmax-eligible	0.0032%	31,225
European (non-Finnish)	0.00161%	62,086
South Asian	0.0011%	90,986

Finnish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Phe1963del
Coding: c.5880CTT[2]
MANE Select: NM_000260
dbSNP: rs111033232
Type: Microsatellite
Location: chr11:77208453 (GRCh38)
Gene constraint: LOEUF 0.995 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.73 · 1 PDB
Residue 1963: the ferm 2 domain; an α-helix

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

Disease context

MYO7A-related disorder

Also linked: Usher syndrome type 1 autosomal recessive nonsyndromic hearing loss 2 retinitis pigmentosa Usher syndrome type 1B

Similar variants

MYO7A p.Asn1182fs Pathogenic/Likely pathogenic ★★ same condition
MYO7A p.Glu1716del Pathogenic/Likely pathogenic ★★ same condition
MYO7A p.Leu1293fs Pathogenic/Likely pathogenic ★★ same condition
MYO7A p.Ser423fs Likely pathogenic ★★ same condition
MYO7A p.Trp47fs Pathogenic/Likely pathogenic ★★ same condition
MYO7A p.Val1501fs Pathogenic/Likely pathogenic ★★ same condition
MYO7A p.Arg1448del Uncertain significance ★★ same condition
MYO7A p.Phe1346del Uncertain significance ★★ 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-phe1963del (accessed [today's date]).

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