Is MYO7A p.Glu1579Lys (c.4735G>A) pathogenic?

MYO7A p.Glu1579Lys (c.4735G>A) is classified Uncertain significance in MYO7A (ClinVar, Multiple submitters, 5 submitters; last evaluated 2025-10-22). AlphaMissense: likely pathogenic (0.8285); Very rare (popmax 0.00667%, amr); Associated with Usher syndrome type 1B.

What condition is associated with MYO7A p.Glu1579Lys (c.4735G>A)?

MYO7A p.Glu1579Lys (c.4735G>A) is associated with Usher syndrome type 1B (ClinVar).

How common is MYO7A p.Glu1579Lys (c.4735G>A) in the general population?

MYO7A p.Glu1579Lys (c.4735G>A) is very rare (popmax 0.00667%, amr) (gnomAD).

What do computational predictors say about MYO7A p.Glu1579Lys (c.4735G>A)?

AlphaMissense predicts likely pathogenic (score 0.8285) — an in-silico prediction, not a clinical call.

MYO7A p.Glu1579Lys

c.4735G>A · rs374766654 · VCV504648

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

AlphaMissense

likely pathogenic

0.8285 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00667%, amr)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Usher syndrome type 1B

Computational evidence

Protein change
AlphaMissense	0.8285	likely pathogenic
REVEL	0.725	pathogenic-leaning
SaProt	LLR -8.27	tolerated
⇒ AlphaMissense and REVEL call this damaging; SaProt does not.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>T here scores Δ0.39 · evaluated, not missing
Constraint at this position
Conservation	phyloP 12	GERP 1.4, phastCons 1
Regional constraint	o/e 0.95	unconstrained · MANE · 84 kb · p 0.0065 · regional, not allelic
Overall
CADD	32.0	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 0.00667% Admixed American · 4/59,960 alleles

Filtering AF 0.00255% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00225%

Overall 0.00304% 49/1,613,532 alleles · very rare exomes 42/1,461,312 · genomes 7/152,220 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00667%	14,990
European (non-Finnish)	0.00339%	29,496
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,594
Remaining individualsnot grpmax-eligible	0.0032%	31,228
East Asian	0.00223%	44,892
South Asian	0.0011%	91,014

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.Glu1579Lys
Coding: c.4735G>A
MANE Select: NM_000260
dbSNP: rs374766654
Type: single nucleotide variant
Location: chr11:77199701 (GRCh38)
Gene constraint: LOEUF 0.995 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.73 · 1 PDB
Residue 1579: 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.Glu1579Ter Pathogenic ★ same residue
MYO7A p.Glu1579Gln Uncertain significance ★ ⚠ same residue
MYO7A p.Glu1579= Likely benign ★ 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

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-glu1579lys (accessed [today's date]).

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