Is MYO7A p.Leu1531Pro (c.4592T>C) pathogenic?

MYO7A p.Leu1531Pro (c.4592T>C) is classified Uncertain significance in MYO7A (ClinVar, Single submitter, 2 submitters; last evaluated 2021-09-01). AlphaMissense: likely benign (0.0635); No allele count reported in gnomAD v4.1 (AN 1,520,484); Associated with Usher syndrome type 1B.

What condition is associated with MYO7A p.Leu1531Pro (c.4592T>C)?

MYO7A p.Leu1531Pro (c.4592T>C) is associated with Usher syndrome type 1B (ClinVar).

How common is MYO7A p.Leu1531Pro (c.4592T>C) in the general population?

MYO7A p.Leu1531Pro (c.4592T>C) is no allele count reported in gnomAD v4.1 (AN 1,520,484) (gnomAD).

What do computational predictors say about MYO7A p.Leu1531Pro (c.4592T>C)?

AlphaMissense predicts likely benign (score 0.0635) — an in-silico prediction, not a clinical call.

MYO7A p.Leu1531Pro

c.4592T>C · rs1956914595 · VCV1023140

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0635 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,520,484)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

Usher syndrome type 1B

Computational evidence

Protein change
AlphaMissense	0.0635	likely benign
REVEL	0.609	indeterminate
SaProt	LLR -6.02	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.5	GERP 1.4, phastCons 1
Regional constraint	o/e 0.95	unconstrained · MANE · 84 kb · p 0.0065 · regional, not allelic
Overall
CADD	21.5	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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

Population frequency

gnomAD v4.1 · exomes + genomes

No allele count reported in gnomAD v4.1 (AN 1,520,484). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: MYO7A
Protein: p.Leu1531Pro
Coding: c.4592T>C
MANE Select: NM_000260
dbSNP: rs1956914595
Type: single nucleotide variant
Location: chr11:77199558 (GRCh38)
Gene constraint: LOEUF 0.995 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.73 · 1 PDB
Residue 1531: 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.Leu1531= 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
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-leu1531pro (accessed [today's date]).

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