Is MYO7A p.Pro694Thr (c.2080C>A) pathogenic?

MYO7A p.Pro694Thr (c.2080C>A) is classified Uncertain significance in MYO7A (ClinVar, Single submitter, 1 submitter; last evaluated 2024-10-23). AlphaMissense: ambiguous (0.5406); Absent from gnomAD v4.1.

How common is MYO7A p.Pro694Thr (c.2080C>A) in the general population?

MYO7A p.Pro694Thr (c.2080C>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about MYO7A p.Pro694Thr (c.2080C>A)?

AlphaMissense predicts ambiguous (score 0.5406) — an in-silico prediction, not a clinical call.

MYO7A p.Pro694Thr

c.2080C>A · rs2135425969 · VCV1347300

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5406 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Computational evidence

Protein change
AlphaMissense	0.5406	ambiguous
REVEL	0.496	indeterminate
SaProt	LLR -12.11	damaging
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 1.6, phastCons 1
Regional constraint	o/e 0.95	unconstrained · MANE · 84 kb · p 0.0065 · regional, not allelic
Overall
CADD	24.0	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: MYO7A
Protein: p.Pro694Thr
Coding: c.2080C>A
MANE Select: NM_000260
dbSNP: rs2135425969
Type: single nucleotide variant
Location: chr11:77174900 (GRCh38)
Gene constraint: LOEUF 0.995 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.73 · 1 PDB
Residue 694: the myosin motor domain

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

Similar variants

MYO7A p.Pro694Leu Uncertain significance ★★ ⚠ same residue
MYO7A p.Pro694= Likely benign ★★ same residue
MYO7A p.Pro694Ala Uncertain significance ★ ⚠ same residue
MYO7A p.Ala1288Pro Likely pathogenic ★★★ same type
MYO7A p.Arg1168Gln Pathogenic ★★★ ⚠ same type
MYO7A p.Arg1873Gln Pathogenic ★★★ ⚠ same type
MYO7A p.Arg395Cys Likely pathogenic ★★★ ⚠ same type
MYO7A p.Arg668Cys Pathogenic ★★★ same type

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-pro694thr (accessed [today's date]).

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