Is MYO7A p.Asp1960Val (c.5879A>T) pathogenic?

MYO7A p.Asp1960Val (c.5879A>T) is classified Uncertain significance in MYO7A (ClinVar, No assertion criteria, 1 submitter; last evaluated 2020-04-17). AlphaMissense: likely pathogenic (0.9855); Ultra-rare (popmax 0.0156%, eas); Associated with Usher syndrome type 1B.

What condition is associated with MYO7A p.Asp1960Val (c.5879A>T)?

MYO7A p.Asp1960Val (c.5879A>T) is associated with Usher syndrome type 1B (ClinVar).

How common is MYO7A p.Asp1960Val (c.5879A>T) in the general population?

MYO7A p.Asp1960Val (c.5879A>T) is ultra-rare (popmax 0.0156%, eas) (gnomAD).

What do computational predictors say about MYO7A p.Asp1960Val (c.5879A>T)?

AlphaMissense predicts likely pathogenic (score 0.9855) — an in-silico prediction, not a clinical call.

MYO7A p.Asp1960Val

c.5879A>T · rs1387553850 · VCV989486

Uncertain significance No assertion criteria

Classification

Uncertain significance

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9855 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0156%, eas)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Usher syndrome type 1B

Computational evidence

Protein change
AlphaMissense	0.9855	likely pathogenic
REVEL	0.861	moderately pathogenic-leaning
SaProt	LLR -2.65	tolerated
⇒ AlphaMissense and REVEL call this damaging; SaProt does not.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · A>G here scores Δ0.26 · evaluated, not missing
Constraint at this position
Conservation	phyloP 11	GERP 1.6, phastCons 1
Regional constraint	o/e 0.95	unconstrained · MANE · 84 kb · p 0.0065 · regional, not allelic
Overall
CADD	24.4	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0156% East Asian · 7/44,878 alleles

Filtering AF 0.00726% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00515%

Overall 0.00062% 10/1,613,408 alleles · ultra-rare exomes 7/1,461,262 · genomes 3/152,146 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0156%	6,411
Remaining individualsnot grpmax-eligible	0.0048%	20,817

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.Asp1960Val
Coding: c.5879A>T
MANE Select: NM_000260
dbSNP: rs1387553850
Type: single nucleotide variant
Location: chr11:77208452 (GRCh38)
Gene constraint: LOEUF 0.995 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.73 · 1 PDB
Residue 1960: the ferm 2 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.Asp1960Tyr Uncertain significance ⚠ same residue
MYO7A p.Asp1960Glu 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

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-asp1960val (accessed [today's date]).

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