Is MYO7A p.Leu855Pro (c.2564T>C) pathogenic?

MYO7A p.Leu855Pro (c.2564T>C) is classified Uncertain significance in MYO7A (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-09-30). AlphaMissense: likely pathogenic (0.855); No allele count reported in gnomAD v4.1 (AN 1,530,784); Associated with hearing loss disorder.

What condition is associated with MYO7A p.Leu855Pro (c.2564T>C)?

MYO7A p.Leu855Pro (c.2564T>C) is associated with hearing loss disorder (ClinVar).

How common is MYO7A p.Leu855Pro (c.2564T>C) in the general population?

MYO7A p.Leu855Pro (c.2564T>C) is no allele count reported in gnomAD v4.1 (AN 1,530,784) (gnomAD).

What do computational predictors say about MYO7A p.Leu855Pro (c.2564T>C)?

AlphaMissense predicts likely pathogenic (score 0.855) — an in-silico prediction, not a clinical call.

MYO7A p.Leu855Pro

c.2564T>C · VCV4277295

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.855 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,530,784)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

hearing loss disorder

Computational evidence

Protein change
AlphaMissense	0.855	likely pathogenic
REVEL	0.623	indeterminate
SaProt	LLR -11.11	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.8	GERP 1.8, phastCons 1
Regional constraint	o/e 0.95	unconstrained · MANE · 84 kb · p 0.0065 · regional, not allelic
Overall
CADD	24.8	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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 1,530,784). 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.Leu855Pro
Coding: c.2564T>C
MANE Select: NM_000260
Type: single nucleotide variant
Location: chr11:77179931 (GRCh38)
Gene constraint: LOEUF 0.995 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.73 · 1 PDB
Residue 855: the iq 5 domain

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

Disease context

hearing loss disorder — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

MYO7A p.Leu855= Likely benign ★ same residue
MYO7A c.4442-1G>C Pathogenic/Likely pathogenic ★★ same condition
MYO7A p.Ala1005Val Uncertain significance ★★ ⚠ same condition
MYO7A p.Ala598Thr Uncertain significance ★★ same condition
MYO7A p.Ala889Val Uncertain significance ★★ ⚠ same condition
MYO7A p.Arg1967Gln Uncertain significance ★★ ⚠ same condition
MYO7A p.Arg467Trp Uncertain significance ★★ same condition
MYO7A p.Arg796Trp 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-leu855pro (accessed [today's date]).

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