Is MYO7B p.Gln1798Pro (c.5393A>C) pathogenic?

MYO7B p.Gln1798Pro (c.5393A>C) is classified Uncertain significance in MYO7B (ClinVar, Single submitter, 1 submitter; last evaluated 2023-02-16). AlphaMissense: likely benign (0.2431); Absent from gnomAD v4.1.

How common is MYO7B p.Gln1798Pro (c.5393A>C) in the general population?

MYO7B p.Gln1798Pro (c.5393A>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about MYO7B p.Gln1798Pro (c.5393A>C)?

AlphaMissense predicts likely benign (score 0.2431) — an in-silico prediction, not a clinical call.

MYO7B p.Gln1798Pro

c.5393A>C · rs1380732447 · VCV2486092

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2431 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2431	likely benign
REVEL	0.795	moderately pathogenic-leaning
SaProt	LLR -13.16	damaging
⇒ REVEL and SaProt call this damaging; AlphaMissense does not.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 9.2	GERP 1.3, phastCons 1
Regional constraint	o/e 1.07	unconstrained · MANE · 7,741 bp · p 0.063 · regional, not allelic
Overall
CADD	24.8	PHRED · no single calibrated threshold — expert panels disagree

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

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM Q1772P vs ClinVar Q1798P) — verify the residue.

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: MYO7B
Protein: p.Gln1798Pro
Coding: c.5393A>C
MANE Select: NM_001393586
dbSNP: rs1380732447
Type: single nucleotide variant
Location: chr2:127632389 (GRCh38)
Gene constraint: LOEUF 0.956 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 78.34 · 3 PDB
Residue 1772 UniProt numbering: the myth4 2 domain; the 'mediates interaction with cdhr2, cdhr5 and ush1c' region; an α-helix

Full MYO7B gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

MYO7B p.Thr349Met Uncertain significance ★★ ⚠ same type
MYO7B p.Ile1309Val Benign ★★ same type
MYO7B p.Val1556Ile Benign ★★ same type
MYO7B p.Val1876= Benign ★★ same type
MYO7B p.Ala1010Thr Uncertain significance ★ ⚠ same type
MYO7B p.Ala1092Thr Uncertain significance ★ ⚠ same type
MYO7B p.Ala1109Thr Uncertain significance ★ ⚠ same type
MYO7B p.Ala1126Thr Uncertain significance ★ ⚠ 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/myo7b-p-gln1798pro (accessed [today's date]).

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